OnCo
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Non-small-cell lung cancer

Non-small-cell lung cancer is the biggest cancer killer, and the proving ground for precision medicine: a dozen targetable mutations, immunotherapy for the rest, and ADCs and bispecifics arriving now.

Non-small-cell lung cancer is ~85% of lung cancer and the leading cause of cancer death worldwide (~1.8 million deaths a year, all lung cancer). Adenocarcinoma (~50%) and squamous cell carcinoma (~25-30%) dominate; large-cell and other histologies make up the rest. Roughly half of adenocarcinomas carry a targetable driver (EGFR ~15% Western/40-50% East Asian, KRAS ~30% Western, ALK ~5%, MET ex14 ~3%, HER2 ~2-3%, BRAF V600E ~2%, RET ~1-2%, ROS1 ~1-2%, NTRK <1%), which makes broad genomic profiling at diagnosis mandatory. Tobacco drives most squamous and KRAS-mutant disease; never-smoker adenocarcinoma, increasingly common in East Asian women, is EGFR- and ALK-enriched.

Care is organised by stage and driver. Low-dose CT screening (NLST, NELSON) cuts mortality but is under-used. Early-stage disease is resected (lobectomy or, for small peripheral tumours, segmentectomy) or ablated with SBRT; perioperative immunotherapy (CheckMate 816, KEYNOTE-671) and adjuvant targeted therapy (ADAURA for EGFR, ALINA for ALK) are standard. Stage III unresectable disease gets chemoradiation followed by durvalumab (PACIFIC) or osimertinib if EGFR-mutant (LAURA). Metastatic driver-positive disease receives a matched TKI or bispecific first (osimertinib or amivantamab-lazertinib; lorlatinib or alectinib; repotrectinib or zidesamtinib; sotorasib or adagrasib after chemo-IO; selpercatinib; capmatinib or tepotinib; zongertinib or sevabertinib; dabrafenib-trametinib), then chemotherapy and ADCs (Dato-DXd approved 2025 in EGFR-mutant disease). Driver-negative metastatic disease gets PD-(L)1 blockade with or without platinum doublets depending on PD-L1 TPS, with tremelimumab-durvalumab-chemotherapy for PD-L1-negative and STK11/KEAP1-altered tumours.

The frontier is fourfold: (1) beating osimertinib and pembrolizumab head-to-head (MARIPOSA succeeded; HARMONi-2 succeeded in China while HARMONi-3 missed its interim PFS analysis in May 2026, with an FDA decision on ivonescimab due 14 November 2026); (2) next-generation TKIs that clear compound resistance (neladalkib PDUFA 27 November 2026; divarasib superior to first-generation KRAS inhibitors in Krascendo 1); (3) ADCs and bispecific ADCs after TKI failure, tempered by HERTHENA-Lung02's failure to improve survival and TROPION-Lung01's mixed result; and (4) earlier intervention via MRD-guided adjuvant therapy, neoadjuvant targeted therapy (NeoADAURA), and AI-assisted screening.

State of the art today

  • First regimen to beat osimertinib (MARIPOSA) and first to beat pembrolizumab (ivonescimab, China).
  • Twelve targetable drivers each have an approved matched therapy; two oral HER2 TKIs (zongertinib, sevabertinib) arrived in 2025-26.
  • First-in-class bispecific ivonescimab beat pembrolizumab on PFS and OS in China; the US decision (PDUFA 14 Nov 2026) hinges on HARMONi.
Show survival figures (7)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

  • 5-year PFS 60% with lorlatinib in ALK+ disease.
  • Adjuvant osimertinib halves death risk.
  • Lorlatinib: 5-year PFS 60% in ALK-positive disease, the longest for any targeted therapy in metastatic solid tumours.
  • Adjuvant osimertinib halves the risk of death (ADAURA, OS HR 0.49); adjuvant alectinib cuts recurrence by 76% (ALINA).
  • Amivantamab + lazertinib is the first regimen to beat osimertinib, with median OS more than 12 months longer (MARIPOSA).
  • Perioperative chemo-immunotherapy improves survival in resectable disease (CheckMate 816, KEYNOTE-671).
  • 5-year survival with pembrolizumab in PD-L1-high disease is ~32%, unthinkable a decade ago.
Who it affects

~85% of lung cancer; lung cancer kills ~1.8 million people a year, more than any other cancer.

Group
lung

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

Site: Trachea, bronchus and lung (shared total; subtype split not reported). World: 2,480,675 new cases, 1,817,469 deaths.

#CountryNew casesDeaths
1China1,060,584733,291
2United States of America226,033127,653
3Japan136,72383,243
4India81,74875,031
5Russian Federation70,36251,887
6Germany62,02547,731
7United Kingdom50,70035,394
8France (metropolitan)49,61336,876
9Brazil44,21338,292
10Italy43,80835,668

GLOBOCAN does not split lung cancer by histology. NSCLC is roughly 85% of lung cancer; figures are for all lung cancer.

Standard of care

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Screening

Annual low-dose CT for high-risk smokers (NLST, NELSON); AI nodule scoring emerging.

NCCN Guidelines: Non-Small Cell Lung Cancer
CT (computed tomography)AI in radiology
Early stage

Surgery or SBRT; perioperative chemo-immunotherapy; adjuvant osimertinib (EGFR) or alectinib (ALK).

NCCN Guidelines: Non-Small Cell Lung Cancer
SBRT / SABR (stereotactic radiotherapy)ADAURAOsimertinib
Stage III unresectable

Chemoradiation → durvalumab (PACIFIC) or osimertinib (LAURA, EGFR).

NCCN Guidelines: Non-Small Cell Lung Cancer
DurvalumabIMRT / IGRT (modern external beam)
Metastatic, driver-positive

Matched TKI or bispecific; ADCs after progression.

ESMO-MCBS · 3 (DESTINY-Lung02, HER2-mutant, second line)
OsimertinibAmivantamabLorlatinibSelpercatinibZongertinibSotorasibDatopotamab deruxtecan
Metastatic, driver-negative

PD-(L)1 ± chemotherapy; docetaxel or ADC/TTFields second line.

NCCN Guidelines: Non-Small Cell Lung Cancer
PembrolizumabNivolumabOptune / Optune Pax (TTFields)
Screening (age 50-80, ≥20 pack-years)

Annual low-dose CT with Lung-RADS reporting; AI nodule scoring emerging; robotic bronchoscopy for peripheral nodule biopsy.

Low-dose CT lung screeningNLST & NELSON (low-dose CT screening)Robotic and navigational bronchoscopyAI in radiology
Stage I-II resectable

Lobectomy or segmentectomy (small peripheral) with nodal staging; SBRT if inoperable. Stage IB-IIIA: neoadjuvant chemo-IO (CheckMate 816) or perioperative chemo-IO (KEYNOTE-671); adjuvant osimertinib if EGFR-mutant (ADAURA), alectinib if ALK-positive (ALINA); adjuvant chemotherapy otherwise for stage II+.

Robotic & minimally invasive surgerySBRT / SABR (stereotactic radiotherapy)CheckMate 816KEYNOTE-671ADAURAALINAOsimertinibAlectinib
Stage III unresectable

Concurrent platinum chemoradiation → durvalumab 1 year (PACIFIC), or osimertinib until progression if EGFR-mutant (LAURA). Proton therapy in selected cases.

IMRT / IGRT (modern external beam)PACIFICLAURADurvalumabOsimertinibProton therapy
Metastatic, EGFR exon 19 del / L858R

First line: osimertinib ± platinum-pemetrexed (FLAURA2) or amivantamab + lazertinib (MARIPOSA, OS benefit). Progression: re-biopsy/ctDNA; amivantamab + chemotherapy (MARIPOSA-2), Dato-DXd (TROPION-Lung05), platinum doublet; MET TKI add-on if MET-amplified; platinum-etoposide if small-cell transformation.

OsimertinibFLAURA2AmivantamabLazertinibMARIPOSAAmivantamab + lazertinib (first-line EGFR NSCLC)Datopotamab deruxtecanTROPION-Lung05EGFR exon 19 deletion & L858REGFR C797SMET amplification (bypass resistance)Histologic transformation
Metastatic, EGFR exon 20 insertion

Amivantamab + platinum-pemetrexed (PAPILLON); sunvozertinib later line.

AmivantamabEGFR exon 20 insertion
Metastatic, ALK-rearranged

Lorlatinib (CROWN; 5-year PFS 60%) or alectinib first line; on progression, neladalkib (under review) or lorlatinib if not used; local therapy for oligoprogression; chemotherapy.

LorlatinibCROWNAlectinibNeladalkibALKOVE-1Oligoprogression
Metastatic, ROS1-rearranged

Repotrectinib or zidesamtinib (2026) first line; entrectinib/crizotinib alternatives.

RepotrectinibZidesamtinibROS1
Metastatic, KRAS G12C

First line: PD-(L)1 ± chemotherapy by PD-L1 (G12C inhibitor + IO combinations in phase 3: olomorasib SUNRAY-01, divarasib Krascendo 2). Second line: sotorasib or adagrasib (CodeBreaK 200, KRYSTAL-12); divarasib superior head-to-head (Krascendo 1, 2026).

SotorasibAdagrasibDivarasibOlomorasibCodeBreaK 200KRYSTAL-12Krascendo 1KRAS & RAS inhibitors
Metastatic, BRAF V600E

Dabrafenib + trametinib or encorafenib + binimetinib first line; chemo-IO as alternative.

Dabrafenib + trametinibEncorafenibBRAF
Metastatic, MET exon 14 skipping

Capmatinib or tepotinib first line; telisotuzumab vedotin for c-Met-overexpressing EGFR-wild-type disease after chemotherapy (accelerated 2025).

Capmatinib & tepotinibTelisotuzumab vedotinTeliMET NSCLC-01MET
Metastatic, RET-fusion

Selpercatinib first line (LIBRETTO-431); pralsetinib alternative.

SelpercatinibLIBRETTO-431PralsetinibRET
Metastatic, HER2-mutant

First line: zongertinib (2026) or chemo-IO; sevabertinib (Nov 2025) or T-DXd after prior therapy.

ZongertinibSevabertinibSOHO-01Trastuzumab deruxtecanHER2
Metastatic, NTRK-fusion

Larotrectinib, entrectinib, or repotrectinib (tumour-agnostic).

RepotrectinibNTRKTumour-agnostic (tissue-agnostic) approval
Metastatic, driver-negative, PD-L1 TPS ≥50%

Pembrolizumab (KEYNOTE-024) or cemiplimab monotherapy; add chemotherapy for high burden or rapid progression. Ivonescimab beat pembrolizumab in China (HARMONi-2); not approved in the US.

PembrolizumabCemiplimabKEYNOTE-024 & KEYNOTE-189IvonescimabHARMONi-2Tumour proportion score (TPS)
Metastatic, driver-negative, PD-L1 TPS <50%

Pembrolizumab + platinum doublet (KEYNOTE-189 non-squamous; KEYNOTE-407 squamous); nivolumab + ipilimumab ± chemotherapy; tremelimumab + durvalumab + chemotherapy for PD-L1-negative or STK11/KEAP1-altered disease. Second line: docetaxel ± ramucirumab, TTFields, or trials of ADCs.

PembrolizumabNivolumabIpilimumabTremelimumabDurvalumabPD-1 blockade + chemotherapy in PD-L1-low NSCLCOptune / Optune Pax (TTFields)
Metastatic, squamous

Pembrolizumab + carboplatin + (nab-)paclitaxel (KEYNOTE-407); no ADC approved (TROPION-Lung01 showed no benefit in squamous); ivonescimab + chemotherapy under study (HARMONi-3).

PembrolizumabPaclitaxel / nab-paclitaxelCarboplatinTROPION-Lung01HARMONi-3

Subtypes & biomarkers

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Subtypes
Biomarkers clinicians test

Target prevalence in this cancer

Target / alterationPrevalenceSource
HER3
EGFR-mutant NSCLC in HERTHENA-Lung01
80-90%
Wikipedia
Folate receptor alpha
70-80%
Wikipedia
TROP2
Adenocarcinoma and squamous
60-70%
PMC
PD-1
20-45%
Wikipedia
KRAS
G12C ~13% of adenocarcinoma
25-30%
cBioPortal (TCGA)
PD-L1
~60-65% TPS >=1%
25-30%
Wikipedia
MAGE-A4
20-30%
Wikipedia
CEACAM5
Non-squamous, CARMEN threshold
20-25%
Wikipedia
PRMT5 (MTAP-deleted cancers)
15%
EGFR
40-50% in East Asian adenocarcinoma
10-15%
cBioPortal (TCGA)
ATR
5-10%
cBioPortal (TCGA)
ALK
Younger never-smokers
3-5%
cBioPortal (TCGA)
MET
Amplification in 5-20% post-EGFR TKI; c-MET overexpression ~25% of non-squamous
3-4%
cBioPortal (TCGA)
BRAF
2-4%
cBioPortal (TCGA)
HER2
2-3%
cBioPortal (TCGA)
RET
1-2%
cBioPortal (TCGA)
TIGIT
n/a
Wikipedia

How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.

History

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  1. 2002Gefitinib approved; dramatic responses in a minority
  2. 2004EGFR mutations explain gefitinib responses
  3. 2004EGFR mutations explain gefitinib responses

    Lynch, Paez, and Pao identify activating EGFR mutations; the birth of lung cancer precision medicine.

    EGFREGFR exon 19 deletion & L858R
  4. 2007EML4-ALK fusion discovered
  5. 2007EML4-ALK fusion discovered

    Soda et al.; crizotinib approved 2011.

    ALK
  6. 2011NLST: CT screening reduces mortality 20%
    CT (computed tomography)
  7. 2011NLST: low-dose CT screening reduces mortality 20%
    NLST & NELSON (low-dose CT screening)Low-dose CT lung screening
  8. 2015Nivolumab beats docetaxel; immunotherapy era
    Nivolumab
  9. 2015Nivolumab beats docetaxel: immunotherapy era

    CheckMate 017/057; pembrolizumab first line for PD-L1 ≥50% follows (KEYNOTE-024, 2016).

    NivolumabPembrolizumabKEYNOTE-024 & KEYNOTE-189
  10. 2017PACIFIC: durvalumab consolidation in stage III
    PACIFICDurvalumab
  11. 2018Osimertinib first line (FLAURA); first tumour-agnostic approval (larotrectinib)
    OsimertinibNTRK
  12. 2020ADAURA: adjuvant osimertinib; MET and RET inhibitors approved
    ADAURACapmatinib & tepotinibSelpercatinibPralsetinib
  13. 2021First KRAS inhibitor (sotorasib)
    Sotorasib
  14. 2021Sotorasib: first KRAS inhibitor; amivantamab for exon 20 insertions
    SotorasibAmivantamabEGFR exon 20 insertion
  15. 2022CheckMate 816: neoadjuvant immunotherapy; tremelimumab-durvalumab (POSEIDON)
    CheckMate 816Tremelimumab
  16. 2023MARIPOSA beats osimertinib; KEYNOTE-671 perioperative IO; ALINA adjuvant alectinib; repotrectinib approved
    MARIPOSAKEYNOTE-671ALINARepotrectinib
  17. 2024LAURA (osimertinib after chemoradiation); HARMONi-2: ivonescimab beats pembrolizumab in China; lazertinib approved
    LAURAHARMONi-2Lazertinib
  18. 2025First MET ADC and first-line amivantamab OS benefit
    Telisotuzumab vedotinMARIPOSA
  19. 2025First MET ADC (telisotuzumab vedotin); Dato-DXd in EGFR-mutant disease; MARIPOSA OS benefit; HER3-DXd BLA withdrawn; zongertinib and sevabertinib approved
    Telisotuzumab vedotinDatopotamab deruxtecanTROPION-Lung05HERTHENA-Lung02ZongertinibSevabertinib
  20. 2026Zongertinib first line; zidesamtinib (ROS1) approved; divarasib beats first-generation KRAS inhibitors; neladalkib and ivonescimab under FDA review
    ZongertinibZidesamtinibKrascendo 1NeladalkibALKOVE-1HARMONi-3

Pipeline

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Under reviewBispecific antibody (PD-1×VEGF)
Ivonescimab
Phase 3Bispecific ADC
Izalontamab brengitecan
Under reviewADC
Sacituzumab tirumotecan
Phase 2Bispecific ADC
Tilatamig samrotecan
Under reviewSmall-molecule pan-RAS(ON) inhibitor
Daraxonrasib · Rasonque
Phase 3ADC
Patritumab deruxtecan
Phase 3Personalised mRNA neoantigen vaccine
Intismeran autogene
ApprovedSmall-molecule kinase inhibitor (ROS1)
Zidesamtinib · Jideytro
Phase 3Small-molecule kinase inhibitor (ALK)
Neladalkib
Phase 3Small-molecule inhibitor (KRAS G12C)
Divarasib
Phase 3Small-molecule inhibitor (KRAS G12C)
Olomorasib
ApprovedSmall-molecule kinase inhibitor (HER2)
Sevabertinib · Hyrnuo
ALKOVE-1Krascendo 1HARMONi-3TeliMET NSCLC-01Low-dose CT lung screeningMRD / molecular residual disease testingAI in radiologyImmuno-PET

Open problems

  • Resistance to every TKI.
  • Squamous histology has few targets.
  • Screening uptake below 20% in the US.
  • Screening uptake is under 20% in the US and lower elsewhere; never-smoker adenocarcinoma has no screening pathway.
  • Resistance to every TKI is near-universal in metastatic disease; C797S has no approved fourth-generation EGFR inhibitor and small-cell transformation is undetectable by ctDNA.
  • Squamous cell carcinoma has almost no targeted options and no approved ADC.
  • KRAS G12C inhibitors add only ~1-2 months of PFS over docetaxel; non-G12C KRAS (G12D, G12V) remains undrugged outside trials.
  • STK11/KEAP1 co-mutated and PD-L1-negative tumours respond poorly to immunotherapy.
  • ADCs after TKI failure have not yet shown a survival benefit over platinum chemotherapy (HERTHENA-Lung02, TROPION-Lung01), and ILD limits combinations.
  • Brain metastases occur in 30-50% of driver-positive patients; CNS activity now drives TKI choice but leptomeningeal disease remains lethal.
  • Global access: most of the world's lung cancer patients never receive genomic profiling.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Non-small-cell lung cancer
condition: non-small cell lung cancer
Open on ClinicalTrials.gov →

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Landmark trials in OnCo

ADAURAALINAALKOVE-1CheckMate 816CodeBreaK 200CROWNFLAURA2HARMONi-2HARMONi-3HERTHENA-Lung02KEYNOTE-024 & KEYNOTE-189KEYNOTE-671Krascendo 1KRYSTAL-12LAURALIBRETTO-431Low-dose olanzapine for cancer anorexia (Tata Memorial)MARIPOSANLST & NELSON (low-dose CT screening)PACIFICPonsegromab phase 2 in cancer cachexiaROMANA 1 and ROMANA 2SOHO-01TeliMET NSCLC-01TROPION-Lung01TROPION-Lung05

Expert centres

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Where the expertise is

Centres linked to this cancer in OnCo

Seeking a second opinion: ask your oncologist for a referral to a high-volume centre; most accept records and pathology by mail or telehealth. In the US, use the NCI's Find a Cancer Center tool or the nonprofit Cancer Commons, which navigates options for advanced cancers at no cost.

Questions to ask

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Bring to your appointment

Questions to ask your oncologist about Non-small-cell lung cancer

Generated from this cancer's standard of care, biomarkers, and pipeline · 61 questions

Newly diagnosed

  1. What is my exact diagnosis, stage, and grade, and which tests established them?
    Why: Everything else follows from an accurate stage and subtype.
  2. Which biomarkers have been tested on my tumour (for example EGFR, ALK, ROS1, BRAF V600E, MET ex14 / amplification / c-MET IHC), and what were the results?
    Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
  3. Which subtype is my cancer, and does that change the recommended treatment?
    Why: Recognised subtypes for this cancer include Adenocarcinoma, Squamous, EGFR-mutant.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Screening

  1. For my situation (screening), which of the standard options do you recommend and why?
    Why: Guideline options include: Annual low-dose CT for high-risk smokers (NLST, NELSON); AI nodule scoring emerging.

Early stage

  1. For my situation (early stage), which of the standard options do you recommend and why?
    Why: Guideline options include: Surgery or SBRT; perioperative chemo-immunotherapy; adjuvant osimertinib (EGFR) or alectinib (ALK).
  2. Am I a candidate for Osimertinib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of ADAURA apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Stage III unresectable

  1. For my situation (stage iii unresectable), which of the standard options do you recommend and why?
    Why: Guideline options include: Chemoradiation → durvalumab (PACIFIC) or osimertinib (LAURA, EGFR).
  2. Am I a candidate for Durvalumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. For my situation (stage iii unresectable), which of the standard options do you recommend and why?
    Why: Guideline options include: Concurrent platinum chemoradiation → durvalumab 1 year (PACIFIC), or osimertinib until progression if EGFR-mutant (LAURA). Proton therapy in selected cases.
  4. Am I a candidate for Durvalumab, Osimertinib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  5. How do the results of PACIFIC and LAURA apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, driver-positive

  1. For my situation (metastatic, driver-positive), which of the standard options do you recommend and why?
    Why: Guideline options include: Matched TKI or bispecific; ADCs after progression.
  2. Am I a candidate for Osimertinib, Amivantamab, Lorlatinib or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Metastatic, driver-negative

  1. For my situation (metastatic, driver-negative), which of the standard options do you recommend and why?
    Why: Guideline options include: PD-(L)1 ± chemotherapy; docetaxel or ADC/TTFields second line.
  2. Am I a candidate for Pembrolizumab, Nivolumab, Optune / Optune Pax (TTFields), and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Screening (age 50-80, ≥20 pack-years)

  1. For my situation (screening (age 50-80, ≥20 pack-years)), which of the standard options do you recommend and why?
    Why: Guideline options include: Annual low-dose CT with Lung-RADS reporting; AI nodule scoring emerging; robotic bronchoscopy for peripheral nodule biopsy.
  2. How do the results of NLST & NELSON (low-dose CT screening) apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Stage I-II resectable

  1. For my situation (stage i-ii resectable), which of the standard options do you recommend and why?
    Why: Guideline options include: Lobectomy or segmentectomy (small peripheral) with nodal staging; SBRT if inoperable. Stage IB-IIIA: neoadjuvant chemo-IO (CheckMate 816) or perioperative chemo-IO (KEYNOTE-671); adjuvant osimertinib if EGFR-mutant (ADAURA), alectinib if ALK-positive (ALINA); adjuvant chemotherapy otherwise for stage II+.
  2. Am I a candidate for Osimertinib, Alectinib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of CheckMate 816 and KEYNOTE-671 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, EGFR exon 19 del / L858R

  1. For my situation (metastatic, egfr exon 19 del / l858r), which of the standard options do you recommend and why?
    Why: Guideline options include: First line: osimertinib ± platinum-pemetrexed (FLAURA2) or amivantamab + lazertinib (MARIPOSA, OS benefit). Progression: re-biopsy/ctDNA; amivantamab + chemotherapy (MARIPOSA-2), Dato-DXd (TROPION-Lung05), platinum doublet; MET TKI add-on if MET-amplified; platinum-etoposide if small-cell transformation.
  2. Am I a candidate for Osimertinib, Amivantamab, Lazertinib or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of FLAURA2 and MARIPOSA apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, EGFR exon 20 insertion

  1. For my situation (metastatic, egfr exon 20 insertion), which of the standard options do you recommend and why?
    Why: Guideline options include: Amivantamab + platinum-pemetrexed (PAPILLON); sunvozertinib later line.
  2. Am I a candidate for Amivantamab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Metastatic, ALK-rearranged

  1. For my situation (metastatic, alk-rearranged), which of the standard options do you recommend and why?
    Why: Guideline options include: Lorlatinib (CROWN; 5-year PFS 60%) or alectinib first line; on progression, neladalkib (under review) or lorlatinib if not used; local therapy for oligoprogression; chemotherapy.
  2. Am I a candidate for Lorlatinib, Alectinib, Neladalkib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of CROWN and ALKOVE-1 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, ROS1-rearranged

  1. For my situation (metastatic, ros1-rearranged), which of the standard options do you recommend and why?
    Why: Guideline options include: Repotrectinib or zidesamtinib (2026) first line; entrectinib/crizotinib alternatives.
  2. Am I a candidate for Repotrectinib, Zidesamtinib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Metastatic, KRAS G12C

  1. For my situation (metastatic, kras g12c), which of the standard options do you recommend and why?
    Why: Guideline options include: First line: PD-(L)1 ± chemotherapy by PD-L1 (G12C inhibitor + IO combinations in phase 3: olomorasib SUNRAY-01, divarasib Krascendo 2). Second line: sotorasib or adagrasib (CodeBreaK 200, KRYSTAL-12); divarasib superior head-to-head (Krascendo 1, 2026).
  2. Am I a candidate for Sotorasib, Adagrasib, Divarasib or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of CodeBreaK 200 and KRYSTAL-12 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, BRAF V600E

  1. For my situation (metastatic, braf v600e), which of the standard options do you recommend and why?
    Why: Guideline options include: Dabrafenib + trametinib or encorafenib + binimetinib first line; chemo-IO as alternative.
  2. Am I a candidate for Dabrafenib + trametinib, Encorafenib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Metastatic, MET exon 14 skipping

  1. For my situation (metastatic, met exon 14 skipping), which of the standard options do you recommend and why?
    Why: Guideline options include: Capmatinib or tepotinib first line; telisotuzumab vedotin for c-Met-overexpressing EGFR-wild-type disease after chemotherapy (accelerated 2025).
  2. Am I a candidate for Capmatinib & tepotinib, Telisotuzumab vedotin, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of TeliMET NSCLC-01 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, RET-fusion

  1. For my situation (metastatic, ret-fusion), which of the standard options do you recommend and why?
    Why: Guideline options include: Selpercatinib first line (LIBRETTO-431); pralsetinib alternative.
  2. Am I a candidate for Selpercatinib, Pralsetinib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of LIBRETTO-431 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, HER2-mutant

  1. For my situation (metastatic, her2-mutant), which of the standard options do you recommend and why?
    Why: Guideline options include: First line: zongertinib (2026) or chemo-IO; sevabertinib (Nov 2025) or T-DXd after prior therapy.
  2. Am I a candidate for Zongertinib, Sevabertinib, Trastuzumab deruxtecan, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of SOHO-01 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, NTRK-fusion

  1. For my situation (metastatic, ntrk-fusion), which of the standard options do you recommend and why?
    Why: Guideline options include: Larotrectinib, entrectinib, or repotrectinib (tumour-agnostic).
  2. Am I a candidate for Repotrectinib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Metastatic, driver-negative, PD-L1 TPS ≥50%

  1. For my situation (metastatic, driver-negative, pd-l1 tps ≥50%), which of the standard options do you recommend and why?
    Why: Guideline options include: Pembrolizumab (KEYNOTE-024) or cemiplimab monotherapy; add chemotherapy for high burden or rapid progression. Ivonescimab beat pembrolizumab in China (HARMONi-2); not approved in the US.
  2. Am I a candidate for Pembrolizumab, Cemiplimab, Ivonescimab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of KEYNOTE-024 & KEYNOTE-189 and HARMONi-2 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Metastatic, driver-negative, PD-L1 TPS <50%

  1. For my situation (metastatic, driver-negative, pd-l1 tps <50%), which of the standard options do you recommend and why?
    Why: Guideline options include: Pembrolizumab + platinum doublet (KEYNOTE-189 non-squamous; KEYNOTE-407 squamous); nivolumab + ipilimumab ± chemotherapy; tremelimumab + durvalumab + chemotherapy for PD-L1-negative or STK11/KEAP1-altered disease. Second line: docetaxel ± ramucirumab, TTFields, or trials of ADCs.
  2. Am I a candidate for Pembrolizumab, Nivolumab, Ipilimumab or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Metastatic, squamous

  1. For my situation (metastatic, squamous), which of the standard options do you recommend and why?
    Why: Guideline options include: Pembrolizumab + carboplatin + (nab-)paclitaxel (KEYNOTE-407); no ADC approved (TROPION-Lung01 showed no benefit in squamous); ivonescimab + chemotherapy under study (HARMONi-3).
  2. Am I a candidate for Pembrolizumab, Paclitaxel / nab-paclitaxel, Carboplatin, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
  3. How do the results of TROPION-Lung01 and HARMONi-3 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Any stage

  1. Are there clinical trials I could join, for example of Ivonescimab, Izalontamab brengitecan, Sacituzumab tirumotecan, Tilatamig samrotecan?
    Why: Trials are how the next standard of care is set; asking early keeps options open.
  2. Would a second opinion at a high-volume centre change anything, and can you help arrange it?
    Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
  3. What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?
    Why: Supportive care improves quality of life and helps patients complete treatment.
  4. I read that “Resistance to every TKI”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “Squamous histology has few targets”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.

Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.

Everything relevant

550top

Direct links plus the targets, companies, and technologies of this cancer's products.

technologies

53
AI in radiologyAnti-angiogenic therapyAntibody-drug conjugate (ADC)Bispecific ADCBispecific antibodiesBone-modifying agents (bisphosphonates, denosumab)Breath and volatile-organic-compound detectionCachexia pharmacotherapy: GDF-15 blockade, anamorelin, olanzapineCachexia-directed therapy (GDF-15 blockade)Cancer-associated thrombosis prevention and treatmentcfDNA fragmentomicsComprehensive genomic profilingCT (computed tomography)Cytotoxic chemotherapyDietary fibre and the gut microbiome for immunotherapy responseDietary supplements during cancer treatment: interactions and harmsEarly integrated palliative careExercise during chemotherapy and radiotherapyFaecal microbiota transplantation for PD-1 non-respondersFluorescence-guided surgeryImmune checkpoint inhibitorsImmuno-PETIMRT / IGRT (modern external beam)Intravesical therapy (BCG, chemotherapy, devices, gene and viral therapy)KRAS & RAS inhibitorsLiquid biopsy (ctDNA)Low-dose CT lung screeningMonoclonal antibodiesMRD / molecular residual disease testingMUSK (Stanford, vision-language pathology)Nutrition support and cachexia managementOncology nutrition assessment and medical nutrition therapyOptical & fluorescence imagingPalliative radiotherapyPARP inhibitorsPersonalised neoantigen (mRNA) vaccinesPlatinum agentsPrehabilitation before cancer surgeryProbiotics, antibiotics and stewardship around immunotherapyProton therapyResistance training and protein for cachexia and sarcopeniaRobotic & minimally invasive surgeryRobotic and navigational bronchoscopySBRT / SABR (stereotactic radiotherapy)Sleep and circadian interventions in cancerSmall-molecule kinase inhibitorsSmoking cessation in cancer patientsSybil (MIT/MGH lung cancer risk from CT)T-cell engagers (bispecific)TIL therapyTopoisomerase-I inhibitors (and ADC payloads)TROP2 PETTumour treating fields (TTFields)

targets

28
ALKATRBRAFCD3CD73 / adenosine axisCEACAM5Claudin 6CTLA-4EGFRFolate receptor alphaHER2HER3KRASMETNectin-4NTRKPARPPD-1PD-L1PRAMEPRMT5 (MTAP-deleted cancers)RETROS1TIGITTIM-3TROP2VEGF / VEGFRVISTA

drugs

74
ApprovedSmall-molecule inhibitor (KRAS G12C)
Adagrasib · Krazati
Not mapped hereSmall-molecule pan-ErbB TKI (second generation, irreversible)
Afatinib · Gilotrif / Giotrif
Phase 1Bispecific ADC
AK146D1
ApprovedSmall-molecule kinase inhibitor (ALK)
Alectinib · Alecensa
ApprovedBispecific antibody (EGFR×MET)
Amivantamab · Rybrevant
ApprovedMonoclonal antibody (anti-PD-L1)
Atezolizumab · Tecentriq / Tecentriq Hybreza (SC)
ApprovedMonoclonal antibody (anti-VEGF)
Bevacizumab · Avastin (and biosimilars)
ApprovedSmall-molecule kinase inhibitor (MEK1/2)
Binimetinib · Mektovi
Phase 3ImmTAC (PRAME TCR × CD3 bispecific)
Brenetafusp
Not mapped hereSmall-molecule ALK/EGFR TKI (second generation)
Brigatinib · Alunbrig
Under reviewMonoclonal antibody (anti-PD-1)
Camrelizumab · AiRuiKa
ApprovedSmall-molecule kinase inhibitors (MET)
Capmatinib & tepotinib · Tabrecta / Tepmetko
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
ApprovedMonoclonal antibody (anti-PD-1)
Cemiplimab · Libtayo
Not mapped hereSmall-molecule ALK TKI (second generation)
Ceritinib · Zykadia
ApprovedCytotoxic chemotherapy (platinum)
Cisplatin · Platinol (generic)
Not mapped hereSmall-molecule ALK/ROS1/MET TKI (first generation)
Crizotinib · Xalkori
ApprovedSmall-molecule kinase inhibitors (BRAF + MEK)
Dabrafenib + trametinib · Tafinlar + Mekinist
Not mapped hereSmall-molecule pan-ErbB TKI (second generation, irreversible)
Dacomitinib · Vizimpro
Under reviewSmall-molecule pan-RAS(ON) inhibitor
Daraxonrasib · Rasonque
ApprovedADC
Datopotamab deruxtecan · Datroway
Phase 3Small-molecule inhibitor (KRAS G12C)
Divarasib
ApprovedCytotoxic chemotherapy (taxane)
Docetaxel · Taxotere (generic)
ApprovedMonoclonal antibody (anti-PD-L1)
Durvalumab · Imfinzi
Phase 2Small-molecule RAS(ON) G12C-selective inhibitor
Elironrasib
ApprovedSmall-molecule kinase inhibitor (BRAF)
Encorafenib · Braftovi
Not mapped hereSmall-molecule ALK TKI (second generation)
Ensartinib · Ensacove
Not mapped hereSmall-molecule TRK/ROS1/ALK TKI (CNS-penetrant)
Entrectinib · Rozlytrek
Not mapped hereSmall-molecule EGFR TKI (first generation, reversible)
Erlotinib · Tarceva
Not mapped hereSmall-molecule EGFR TKI (first generation, reversible)
Gefitinib · Iressa
Not mapped hereNucleoside analogue (deoxycytidine)
Gemcitabine · Gemzar / Infugem
NegativeSmall molecule (claimed PARP inhibitor)
Iniparib
Phase 3Personalised mRNA neoantigen vaccine
Intismeran autogene
ApprovedMonoclonal antibody (anti-CTLA-4)
Ipilimumab · Yervoy
Under reviewBispecific antibody (PD-1×VEGF)
Ivonescimab
Phase 3Bispecific ADC
Izalontamab brengitecan
Not mapped hereSmall-molecule pan-TRK inhibitor (first generation)
Larotrectinib · Vitrakvi
ApprovedSmall-molecule kinase inhibitor (EGFR)
Lazertinib · Lazcluze
ApprovedTIL cell therapy
Lifileucel · Amtagvi
ApprovedSmall-molecule kinase inhibitor (ALK/ROS1)
Lorlatinib · Lorbrena
WithdrawnSmall-molecule EGFR exon 20 insertion TKI (irreversible)
Mobocertinib · Exkivity
Phase 3Small-molecule kinase inhibitor (ALK)
Neladalkib
ApprovedMonoclonal antibody (anti-PD-1)
Nivolumab · Opdivo / Opdivo Qvantig (SC)
Phase 3Small-molecule inhibitor (KRAS G12C)
Olomorasib
ApprovedDevice (tumour treating fields)
Optune / Optune Pax (TTFields) · Optune
ApprovedSmall-molecule kinase inhibitor (EGFR)
Osimertinib · Tagrisso
ApprovedCytotoxic chemotherapy (taxane)
Paclitaxel / nab-paclitaxel · Taxol / Abraxane
Not mapped hereFolate receptor-targeted near-infrared fluorescent imaging agent
Pafolacianine · Cytalux
Phase 3ADC
Patritumab deruxtecan
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
ApprovedCytotoxic (antifolate)
Pemetrexed · Alimta (and generics)
ApprovedSmall-molecule kinase inhibitor (RET)
Pralsetinib · Gavreto
ApprovedMonoclonal antibody (anti-VEGFR2)
Ramucirumab · Cyramza
ApprovedSmall-molecule kinase inhibitor (ROS1 / NTRK)
Repotrectinib · Augtyro
Under reviewADC
Sacituzumab tirumotecan
ApprovedSmall-molecule kinase inhibitor (RET)
Selpercatinib · Retevmo
ApprovedSmall-molecule kinase inhibitor (HER2)
Sevabertinib · Hyrnuo
EstablishedTumour-informed ctDNA MRD test
Signatera
ApprovedSmall-molecule inhibitor (KRAS G12C)
Sotorasib · Lumakras
Not mapped hereSmall-molecule EGFR exon 20 insertion TKI (irreversible)
Sunvozertinib · Zegfrovy
Not mapped hereSmall-molecule ROS1 TKI (next generation, CNS-penetrant)
Taletrectinib · Ibtrozi
ApprovedADC
Telisotuzumab vedotin · Emrelis
Phase 2Bispecific ADC
Tilatamig samrotecan
NegativeMonoclonal antibody (anti-TIGIT)
Tiragolumab
ApprovedMonoclonal antibody (anti-PD-1)
Tislelizumab · Tevimbra
ApprovedADC
Trastuzumab deruxtecan · Enhertu
Not mapped hereADC
Trastuzumab rezetecan
ApprovedMonoclonal antibody (anti-CTLA-4)
Tremelimumab · Imjudo
WithdrawnADC
Tusamitamab ravtansine
Not mapped hereSemi-synthetic vinca alkaloid
Vinorelbine · Navelbine
ApprovedBispecific antibody (HER2×HER3)
Zenocutuzumab · Bizengri
ApprovedSmall-molecule kinase inhibitor (ROS1)
Zidesamtinib · Jideytro
Phase 2Small-molecule RAS(ON) G12D-selective inhibitor
Zoldonrasib
ApprovedSmall-molecule kinase inhibitor (HER2)
Zongertinib · Hernexeos

companies

36
AbbVie (incl. ImmunoGen, Capstan)AkesoAmgenAstellasAstraZenecaBayerBeOne Medicines (formerly BeiGene)Boehringer IngelheimBristol Myers SquibbDaiichi SankyoDELFI DiagnosticsEli Lilly (incl. Loxo)Frontier MedicinesImmunocoreIovance BiotherapeuticsJiangsu Hengrui PharmaceuticalsJiangsu Hengrui PharmaceuticalsJohnson & JohnsonLunitMerck & Co. (MSD)MerusModernaNateraNovartisNovocureNuvalentPfizer (incl. Seagen)RegeneronRevolution MedicinesRoche / GenentechSanofiSichuan Kelun-BiotechSummit TherapeuticsSystImmune / Sichuan BiokinTakedaTubulis (Gilead)

institutions

80
Aichi Cancer CenterApollo Hospitals (Apollo Cancer Centres)Auckland City Hospital / Te Pūriri o Te Ora Cancer and Blood ServiceBarts Cancer Institute / Barts Health NHS TrustCancer Center Clínica Universidad de Navarra / CIMACancer Council AustraliaCancer Grand ChallengesCancer Research UK Manchester InstituteCentre hospitalier de l'Université de Montréal (CHUM)Centro Nacional de Investigaciones Oncológicas (CNIO)Chang Gung Memorial HospitalChinese Society of Clinical OncologyDana-Farber Brigham Cancer CenterErasmus MC Cancer InstituteETOP IBCSG Partners FoundationGuangdong Provincial People's HospitalHarold C. Simmons Comprehensive Cancer Center, UT SouthwesternHealthCare Global EnterprisesHenan Cancer HospitalHokkaido University HospitalHospital Universitario 12 de OctubreHunan Cancer HospitalInselspital, Bern University Hospital / University Cancer Center InselspitalInstituto Alexander FlemingInstituto Nacional de Câncer (INCA)Instituto Nacional de Cancerología (Mexico)Intergroupe Francophone de Cancérologie ThoraciqueInternational Association for the Study of Lung CancerIRCCS Azienda Ospedaliero-Universitaria di Bologna – Policlinico Sant'OrsolaIRCCS Humanitas Research HospitalIRCCS Regina Elena National Cancer InstituteIstanbul University Institute of OncologyIstituto Nazionale Tumori IRCCS Fondazione G. PascaleJapan Clinical Oncology Group (JCOG)King Hussein Cancer CenterKoo Foundation Sun Yat-Sen Cancer CenterKorean Cancer Study GroupKyoto University HospitalKyushu University HospitalLaura and Isaac Perlmutter Cancer Center at NYU Langone HealthLausanne University Hospital (CHUV) / Ludwig Institute LausanneMaria Skłodowska-Curie National Research Institute of OncologyMarkey Cancer Center, University of KentuckyMUSC Hollings Cancer CenterNational Cancer Center Hospital EastNational Cancer Center KoreaNational Cancer Centre SingaporeNational Taiwan University HospitalNational University Hospital / National University Cancer Institute, SingaporeOsaka International Cancer InstitutePrince of Wales Hospital / Chinese University of Hong KongQueen Mary Hospital / University of Hong KongRajiv Gandhi Cancer Institute and Research CentreRigshospitalet – Copenhagen University HospitalSeoul National University HospitalShandong Cancer Hospital and InstituteShanghai Chest HospitalShanghai Pulmonary HospitalShizuoka Cancer CenterStand Up To CancerTaipei Veterans General HospitalThe Francis Crick InstituteTohoku University HospitalTROG Cancer ResearchUC Davis Comprehensive Cancer CenterUniklinik Köln (CIO)Union Hospital, Tongji Medical CollegeUniversity College London Hospitals / UCL Cancer InstituteUniversity Hospital Basel / Tumour CentreUniversity Hospital Southampton / Centre for Cancer ImmunologyUniversity Hospital Zurich / Comprehensive Cancer Center ZurichUniversity of Colorado Cancer CenterUniversity of Hawai'i Cancer CenterVanderbilt-Ingram Cancer CenterVCU Massey Comprehensive Cancer CenterVelindre Cancer CentreVietnam National Cancer Hospital (K Hospital)West Japan Oncology GroupWinship Cancer Institute of Emory UniversityZhejiang Cancer Hospital

pathways

12
Cancer cachexiaEpithelial–mesenchymal transition & drug effluxField cancerisationKEAP1–NRF2 antioxidant pathwayLineage plasticity & neuroendocrine transformationPD-1 / PD-L1 immune checkpoint & T-cell activationPI3K / AKT / mTORRAS / RAF / MEK / ERK (MAPK)Receptor tyrosine kinase activationSWI/SNF chromatin remodellingThe blood–brain barrier & brain metastasisVEGF angiogenesis

terms

33
AdenocarcinomaAdenocarcinomaBRAF V600E mutationBrain metastases (intracranial disease)Bronchoscopy (EBUS, robotic navigation)Cancer cachexiaChemoradiation (chemoradiotherapy, CRT)Consolidation therapyDifferentiationEGFR C797SEGFR exon 19 deletion & L858REGFR exon 20 insertionEGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M)HER2-positive (IHC 3+ or ISH-amplified)Histologic transformationKRAS mutation subtypes (G12C, G12D, G12V)LobectomyMaintenance therapyMaintenance therapyMalignant pleural effusion and ascitesMediastinumMET amplification (bypass resistance)OligoprogressionPleuraPleurodesis and indwelling pleural catheterPneumonectomyResectable, borderline resectable and unresectableSegmentectomy (sublobar resection)Squamous cell carcinomaSquamous cell carcinoma (SCC)STK11 / KEAP1 co-mutationsTumour proportion score (TPS)Tumour-agnostic (tissue-agnostic) approval

trials

26
ADAURAALINAALKOVE-1CheckMate 816CodeBreaK 200CROWNFLAURA2HARMONi-2HARMONi-3HERTHENA-Lung02KEYNOTE-024 & KEYNOTE-189KEYNOTE-671Krascendo 1KRYSTAL-12LAURALIBRETTO-431Low-dose olanzapine for cancer anorexia (Tata Memorial)MARIPOSANLST & NELSON (low-dose CT screening)PACIFICPonsegromab phase 2 in cancer cachexiaROMANA 1 and ROMANA 2SOHO-01TeliMET NSCLC-01TROPION-Lung01TROPION-Lung05

pairings

10
ADC + checkpoint inhibitorAmivantamab + lazertinib (first-line EGFR NSCLC)BRAF inhibitor + MEK inhibitorCaution: TIGIT + PD-(L)1 blockadeEGFR TKI → ADC on progressionPD-1 blockade + chemotherapy in PD-L1-low NSCLCPD-1 blockade + VEGF inhibitionRadiotherapy + immunotherapySequence: targeted therapy before immunotherapy in driver-positive NSCLCTROP2 PET → TROP2 ADC selection

roadmaps

4
ADC roadmap: from Mylotarg to bispecific and dual-payload ADCsImmunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunityKRAS roadmap: undruggable → G12C → pan-RASTROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET

ideas

83
A cheap old tablet to restore appetiteA clone report from blood at every treatment cycleA coordinated FLASH radiotherapy evidence programme with shared dose-rate standardsA delivery-science moonshot for prevention we already ownA standard platform to get drugs into the brain: focused ultrasound plus shuttle-engineered therapeuticsA standing platform for testing new drugs with radiotherapyA test to tell true oligometastatic disease from hidden widespread spreadAdd a drug when the blood test turns, without stopping the one that worksAdd the second drug on day one when the escape route is predictableAI clears the normal lung screening scans so radiologists read only the suspicious onesAI malignancy scores to end repeat scans and biopsies for benign lung nodulesAutomatic palliative care referral triggered by diagnosis, not by declineAutonomous closed-loop adaptive therapy driven by blood tests and evolutionary modelsBank three spatially separate tumour blocks from every resectionBiopsy the one lesion that is growing while the others shrinkBlock the complement signal that recruits tumour-protecting cellsBlunt the inflammation that wakes sleeping cancer cellsBorrow from past control arms to shrink the control group in phase 3Brain metastases included by default in every solid-tumour trialBuild a human model of the barrier that guards the brain fluidBurden-weighted portfolio targets for every major cancer funderCapture diet, fibre and antibiotic exposure in every immunotherapy pivotal trialCatch wasting early with a smart scale and a step counterCD8 PET to stop or switch immunotherapy earlyCombine the new anti-wasting antibody with exercise and proteinCompeting sponsors share one control arm in the same indicationConfirm low-dose olanzapine for appetite and weight in advanced cancer worldwideConfirm or refute the harm of antioxidant supplements during chemotherapyConfirm ultra-low-dose immunotherapy so it can be afforded where most patients livectDNA-guided dose holidays for lung cancer targeted therapyDedicated cohorts for patients with performance status 2 in first-line trialsDetect tumours changing cell type from RNA in the bloodEvaluate clean-air policies using lung cancer in never-smokersEvery lung screening visit includes stop-smoking medicine, opt-outEvery routine CT scan checked by AI for early cancer signs, with a tracked follow-up pathwayExtended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stableGet the one approved appetite drug licensed beyond a single countryGive immunotherapy in the morningIntercept cancer at the field stageKill drug-tolerant persisters through ferroptosisLook for the resistant sub-population before the first doseLung screening eligibility by risk score, not pack-years, including high-risk never-smokersMake bespoke mouse cancer models in weeks with in vivo gene editingMake cigarettes non-addictive by capping their nicotineMandatory radon testing when homes are sold, with subsidised mitigationMap metabolic dependencies in the patient, not the dishMicrobiome transplant as a routine immunotherapy adjunctMolecular indolence classifiers bundled with every screening programmePathologists order genomic profiling automatically at diagnosis of advanced cancerPause a failed drug so the tumour becomes sensitive to it againPre-surgery platform trials that test combinations on pathological response in monthsPrevention trials aimed only at brain metastasisProtect hearing from cisplatin in adults as we now do in childrenProtect the gut flora of patients about to start immunotherapyPut cytisine, a cheap plant-based quit-smoking pill, on every essential medicines listRandomise a cheap antihistamine alongside immunotherapyRandomised trials of stopping immunotherapy after one year versus continuingRe-test the metastasis, not the old primary, before every change of treatmentSelect cachexia trial patients by the hormone driving their wastingSelect patients for cell therapy by whether their tumour holds reactive T cellsSlow the tumour's mutation engine with APOBEC inhibitors during targeted therapySmoke-free generation laws with a built-in evaluation across countriesSocial impact bonds for cancer prevention, repaid from avoided treatment costsStanding reflex biomarker panels per tumour type, run without an oncologist's orderSwitch drugs at maximum response, not at relapseTake lung screening scanners to supermarket car parks in the poorest areasTest a high-fibre diet as an immunotherapy adjunctTest alternating drug schedules against giving both drugs at onceTest intermittent dosing of targeted drugs to delay resistance, with honest priorsTest protein and resistance training during immunotherapyTreat brain metastases as a disease with its own trials programmeTreat cachexia as a disease: GDF-15 blockade plus anabolic and nutrition bundlesTreat cachexia before it startsTreat immunotherapy side-effects without wiping out the responseTROP2 PET to choose and sequence TROP2 ADCsTurn a brake back on: drugs that reactivate the PP2A phosphataseUnmask hidden antigens with a short epigenetic course before immunotherapyUse a blood test at six weeks to decide whether to keep goingUse a hypoxia scan to pick patients for adenosine-pathway drugsUse the brain's own transport door to carry antibody drugs acrossUse tumour DNA in blood to decide when to pause treatment in metastatic cancerVideo palliative care as an equivalent default option for patients far from a teamWatch the immune system's response in the blood three weeks in

collections

1
LUNGevity Foundation (and GO2 for Lung Cancer)

people

67
Alexander DrilonAnne C. ChiangAsh A. AlizadehBenjamin BesseBenjamin SolomonBob T. LiByoung Chul ChoCaicun ZhouCharles SwantonCharu AggarwalDae Ho LeeDaniel A. HaberDong-Wan KimDongsheng TuEnriqueta FelipEric B. HauraEverett E. VokesFabrice BarlesiFiona BlackhallFrank McCormickHaruhiko FukudaHeather A. WakeleeHelena A. YuHye Ryun KimJean-Charles SoriaJie HeJie WangJohn V. HeymachJulie R. BrahmerJürgen WolfJustin F. GainorKathy S. AlbainKevan M. ShokatKoichi GotoKumar PrabhashLecia V. SequistLi ZhangMatthew MeyersonMaximilian DiehnMiriam MeradMyung-Ju AhnNatasha B. LeighlNathan A. PennellPasi A. JännePatrick M. FordePilar GarridoPrimo N. Lara Jr.Ramaswamy GovindanReinhard BüttnerRoman ThomasSe-Hoon LeeShun LuSolange PetersStephen B. BaylinSuzanne L. TopalianTakashi KohnoTasuku HonjoThomas J. Lynch Jr.Timothy A. ChanVanita NoronhaWeimin LiWenfeng FangWoong-Yang ParkYi-Long WuYou LuYuankai ShiYuichiro Ohe

bottlenecks

23
Acquired resistance to every therapyAI that is built but not validated or deployedBiomarkers are not validated or standardisedCachexia, toxicity and the limits of the patientDormant cells and minimal residual diseaseFragmented care and guideline gapsFunding follows fashion, not burdenIncentives reward me-too drugs and marginal gainsKnowledge reaches practice too slowlyMetastasis is understood least and studied lastMisinformation and unproven therapiesMost lethal cancers are found lateNo one can predict who responds to immunotherapyOlder and multimorbid patients are excluded and undertreatedOverdiagnosis and false alarmsPain relief and palliative care are unavailable to mostPrevention we already have is not deployedThe brain: barrier and sanctuaryThe undruggable driversToo many combinations to testTrials do not represent the people who get cancerTumour heterogeneity and clonal evolutionWrong doses

key papers

19
ADAURA: three years of osimertinib after surgery for EGFR-mutated lung cancerASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitorsCheckMate 816: three cycles of nivolumab plus chemotherapy before lung cancer surgeryCodeBreaK 200: sotorasib versus docetaxel in KRAS G12C-mutated lung cancer, a modest win for the first KRAS drugCROWN: lorlatinib versus crizotinib as first treatment for ALK-positive lung cancerDoll and Hill 1950: the case-control study that tied smoking to lung cancerFifty years of the British Doctors Study: smokers lose ten years of life, quitting gives most of it backFLAURA: osimertinib as first treatment for EGFR-mutated lung cancerHARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancerKEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutationMARIPOSA: amivantamab plus lazertinib versus osimertinib as first treatment for EGFR-mutated lung cancerNELSON: volume-based CT screening reduces lung cancer deaths with fewer false alarmsNLST: yearly low-dose CT scans cut lung cancer deaths in heavy smokersOstrem and Shokat: the hidden pocket that made KRAS G12C druggablePACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancerTemel: early palliative care alongside chemotherapy improved quality of life, mood and survival in lung cancerTopalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancerTRACERx 421: the full-cohort picture of how lung cancer evolves and which subclones drive relapseTRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse

journals

1
Journal of Thoracic Oncology

Key papers

19top
rctThe Lancet 2025
HARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancer

For the first time a new drug has beaten pembrolizumab, the global first-line standard, in a randomised lung cancer trial, and it did so by combining checkpoint blockade with anti-angiogenesis in one molecule. For patients outside China nothing changes yet: the drug is not approved in the West, the trial was single-country, and survival benefit has not been shown. If confirmed in the global HARMONi-3 and HARMONi-7 trials, PD-1 x VEGF bispecifics could replace PD-1 antibodies as the immunotherapy backbone.

rctNew England Journal of Medicine 2024changed practice
MARIPOSA: amivantamab plus lazertinib versus osimertinib as first treatment for EGFR-mutated lung cancer

Patients newly diagnosed with EGFR-mutated advanced lung cancer now have a first-line option that improves survival over osimertinib, particularly if they have high-risk features. The trade-off is intravenous (now subcutaneous) infusions and considerably more skin, nail and clotting toxicity, so osimertinib alone remains reasonable for those who prioritise convenience and tolerability. Both this regimen and osimertinib plus chemotherapy (FLAURA2) are approved; there is no direct comparison.

rctThe Lancet 2023changed practice
CodeBreaK 200: sotorasib versus docetaxel in KRAS G12C-mutated lung cancer, a modest win for the first KRAS drug

Patients with KRAS G12C lung cancer that has progressed after chemo-immunotherapy can take an oral KRAS inhibitor instead of docetaxel and gain a somewhat longer time to progression with fewer severe side effects, but should understand that most tumours become resistant within a year and that survival is not improved. KRAS G12C testing is worthwhile, but first-generation inhibitors are a step rather than a cure; combinations and next-generation inhibitors are the active research fronts.

translationalNature 2023
TRACERx 421: the full-cohort picture of how lung cancer evolves and which subclones drive relapse

Relapse after surgery is driven by particular subclones that can be identified in the primary tumour and tracked in blood, which argues for evolution-aware adjuvant strategies. The pollution finding reframes carcinogenesis: some agents promote already-mutant cells rather than causing mutations.

rctNew England Journal of Medicine 2022changed practice
CheckMate 816: three cycles of nivolumab plus chemotherapy before lung cancer surgery

Patients with operable stage II-III lung cancer without EGFR or ALK alterations should have chemo-immunotherapy discussed before surgery rather than only afterwards. Three pre-operative cycles do not compromise the operation and improve cure rates. Whether to continue immunotherapy after surgery, as the perioperative trials do, and whether patients with pCR need any further treatment, remain open questions.

guidelineJournal of Clinical Oncology 2021changed practice
ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors

Checkpoint inhibitors are now given to hundreds of thousands of patients a year, many in community clinics and emergency departments, so a common, explicit playbook for their autoimmune side effects saves lives. The guideline standardised when to stop, when to give steroids and when to escalate, and made multidisciplinary toxicity teams routine. It does not remove the judgement needed for rare events or for patients whose cancer is responding.

rctNew England Journal of Medicine 2020changed practice
ADAURA: three years of osimertinib after surgery for EGFR-mutated lung cancer

Every resected non-squamous lung cancer should be tested for EGFR mutations, because patients who carry one live longer if they take osimertinib for three years after surgery. The trial does not tell us whether adjuvant chemotherapy can be omitted, nor what happens on relapse after osimertinib, and the three-year duration was chosen empirically.

rctNew England Journal of Medicine 2020changed practice
CROWN: lorlatinib versus crizotinib as first treatment for ALK-positive lung cancer

For ALK-positive advanced lung cancer, lorlatinib as the first drug offers the possibility of many years without progression and strong protection against brain metastases. Alectinib and brigatinib remain alternatives with a gentler side-effect profile; the choice weighs lorlatinib's cognitive, metabolic and weight effects against its unmatched duration of control.

rctNew England Journal of Medicine 2020changed practice
NELSON: volume-based CT screening reduces lung cancer deaths with fewer false alarms

Lung screening works when it uses volumetric nodule management, and it works against a no-screening control. The protocol underpins the UK Targeted Lung Health Check programme and European recommendations. Benefit in women remains less precisely estimated.

rctNew England Journal of Medicine 2018changed practice
FLAURA: osimertinib as first treatment for EGFR-mutated lung cancer

Anyone diagnosed with advanced lung cancer should have EGFR testing before treatment, because osimertinib as the first drug gives the longest disease control, protects the brain, and is well tolerated. Chemotherapy is not the first step for these patients. The remaining questions are whether to intensify upfront (adding chemotherapy or amivantamab) and how to treat resistance when it develops.

rctNew England Journal of Medicine 2018changed practice
KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation

Most patients with newly diagnosed advanced non-squamous lung cancer that lacks a targetable mutation should receive chemotherapy plus pembrolizumab; those with PD-L1 of 50% or more may reasonably receive pembrolizumab alone. About one in five patients is alive at five years, compared with roughly one in ten with chemotherapy alone. Patients with EGFR or ALK alterations were excluded and should have targeted therapy first.

rctNew England Journal of Medicine 2017changed practice
PACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancer

Patients with stage III lung cancer that cannot be removed surgically should receive a year of durvalumab after completing chemoradiotherapy, provided they have not progressed. This roughly doubles the chance of being alive without progression at five years. Whether the benefit extends to PD-L1-negative tumours is contested, and the EGFR-mutated subgroup is better served by osimertinib (LAURA).

translationalNew England Journal of Medicine 2017
TRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse

Lung cancers keep evolving after they form, and it is ongoing chromosomal instability rather than the number of mutations that best predicts who will relapse. This gives a rationale for targeting the earliest (clonal) drivers and neoantigens and for tracking evolution in blood after surgery.

basicNature 2013
Ostrem and Shokat: the hidden pocket that made KRAS G12C druggable

The most frequently mutated oncogene in cancer stopped being undruggable, and patients with KRAS G12C lung and bowel cancers now have targeted pills. The approach, exploiting a mutation-created chemical handle and an inactive-state pocket, has become a template for other hard targets.

translationalNew England Journal of Medicine 2012changed practice
Topalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancer

This study is why PD-1 inhibitors were developed across cancers rather than in melanoma alone: unexpected activity in lung cancer, historically thought immune-resistant, changed drug development priorities industry-wide. It also introduced PD-L1 immunohistochemistry as a candidate biomarker and pneumonitis as a signature toxicity. Within five years PD-1 blockade was approved in more than ten cancers.

rctNew England Journal of Medicine 2011changed practice
NLST: yearly low-dose CT scans cut lung cancer deaths in heavy smokers

For people with a heavy smoking history, an annual low-dose CT scan is one of the few screening tests proven to reduce cancer deaths. Most abnormal scans are not cancer, so screening must be paired with careful nodule management. It does not apply to never-smokers or light smokers.

rctNew England Journal of Medicine 2010changed practice
Temel: early palliative care alongside chemotherapy improved quality of life, mood and survival in lung cancer

Palliative care is not what happens when treatment stops; it works best alongside cancer treatment from the start. Patients feel better, are less depressed and may live longer. Access remains the constraint: most of the world's patients never see a palliative care specialist.

observationalBMJ 2004changed practice
Fifty years of the British Doctors Study: smokers lose ten years of life, quitting gives most of it back

Smoking is the single largest preventable cause of cancer death, and quitting at any age helps, with the greatest gain from quitting young. Cessation support belongs in every cancer service, including lung screening programmes.

observationalBMJ 1950changed practice
Doll and Hill 1950: the case-control study that tied smoking to lung cancer

Doll and Hill's 1950 study is where the evidence that smoking causes cancer begins. Everything from cigarette warnings and tax to smoke-free laws and lung screening eligibility descends from this study and the cohort that followed it.

Latest papers

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Latest papers · live from Europe PMC
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Query for this cancer: (TITLE:"Non-small-cell lung cancer" OR ABSTRACT:"Non-small-cell lung cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Non-small-cell lung cancer, not a curated reading list.

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Pages like this

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technologies

44
AI in radiologyAntibody-drug conjugate (ADC)Bispecific ADCBispecific antibodiesBone-modifying agents (bisphosphonates, denosumab)Breath and volatile-organic-compound detectionCachexia pharmacotherapy: GDF-15 blockade, anamorelin, olanzapineCachexia-directed therapy (GDF-15 blockade)Cancer-associated thrombosis prevention and treatmentcfDNA fragmentomicsComprehensive genomic profilingCT (computed tomography)Dietary fibre and the gut microbiome for immunotherapy responseDietary supplements during cancer treatment: interactions and harmsEarly integrated palliative careExercise during chemotherapy and radiotherapyFaecal microbiota transplantation for PD-1 non-respondersImmune checkpoint inhibitorsImmuno-PETIMRT / IGRT (modern external beam)KRAS & RAS inhibitorsLiquid biopsy (ctDNA)Low-dose CT lung screeningMRD / molecular residual disease testingMUSK (Stanford, vision-language pathology)Nutrition support and cachexia managementOncology nutrition assessment and medical nutrition therapyPalliative radiotherapyPersonalised neoantigen (mRNA) vaccinesPlatinum agentsPrehabilitation before cancer surgeryProbiotics, antibiotics and stewardship around immunotherapyProton therapyResistance training and protein for cachexia and sarcopeniaRobotic & minimally invasive surgeryRobotic and navigational bronchoscopySBRT / SABR (stereotactic radiotherapy)Sleep and circadian interventions in cancerSmall-molecule kinase inhibitorsSmoking cessation in cancer patientsSybil (MIT/MGH lung cancer risk from CT)TIL therapyTROP2 PETTumour treating fields (TTFields)

targets

25
ALKATRBRAFCD73 / adenosine axisCEACAM5Claudin 6CTLA-4EGFRFolate receptor alphaHER2HER3KRASMETNTRKPD-1PD-L1PRAMEPRMT5 (MTAP-deleted cancers)RETROS1TIGITTIM-3TROP2VEGF / VEGFRVISTA

drugs

74
ApprovedSmall-molecule inhibitor (KRAS G12C)
Adagrasib · Krazati
Not mapped hereSmall-molecule pan-ErbB TKI (second generation, irreversible)
Afatinib · Gilotrif / Giotrif
Phase 1Bispecific ADC
AK146D1
ApprovedSmall-molecule kinase inhibitor (ALK)
Alectinib · Alecensa
ApprovedBispecific antibody (EGFR×MET)
Amivantamab · Rybrevant
ApprovedMonoclonal antibody (anti-PD-L1)
Atezolizumab · Tecentriq / Tecentriq Hybreza (SC)
ApprovedMonoclonal antibody (anti-VEGF)
Bevacizumab · Avastin (and biosimilars)
ApprovedSmall-molecule kinase inhibitor (MEK1/2)
Binimetinib · Mektovi
Phase 3ImmTAC (PRAME TCR × CD3 bispecific)
Brenetafusp
Not mapped hereSmall-molecule ALK/EGFR TKI (second generation)
Brigatinib · Alunbrig
Under reviewMonoclonal antibody (anti-PD-1)
Camrelizumab · AiRuiKa
ApprovedSmall-molecule kinase inhibitors (MET)
Capmatinib & tepotinib · Tabrecta / Tepmetko
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
ApprovedMonoclonal antibody (anti-PD-1)
Cemiplimab · Libtayo
Not mapped hereSmall-molecule ALK TKI (second generation)
Ceritinib · Zykadia
ApprovedCytotoxic chemotherapy (platinum)
Cisplatin · Platinol (generic)
Not mapped hereSmall-molecule ALK/ROS1/MET TKI (first generation)
Crizotinib · Xalkori
ApprovedSmall-molecule kinase inhibitors (BRAF + MEK)
Dabrafenib + trametinib · Tafinlar + Mekinist
Not mapped hereSmall-molecule pan-ErbB TKI (second generation, irreversible)
Dacomitinib · Vizimpro
Under reviewSmall-molecule pan-RAS(ON) inhibitor
Daraxonrasib · Rasonque
ApprovedADC
Datopotamab deruxtecan · Datroway
Phase 3Small-molecule inhibitor (KRAS G12C)
Divarasib
ApprovedCytotoxic chemotherapy (taxane)
Docetaxel · Taxotere (generic)
ApprovedMonoclonal antibody (anti-PD-L1)
Durvalumab · Imfinzi
Phase 2Small-molecule RAS(ON) G12C-selective inhibitor
Elironrasib
ApprovedSmall-molecule kinase inhibitor (BRAF)
Encorafenib · Braftovi
Not mapped hereSmall-molecule ALK TKI (second generation)
Ensartinib · Ensacove
Not mapped hereSmall-molecule TRK/ROS1/ALK TKI (CNS-penetrant)
Entrectinib · Rozlytrek
Not mapped hereSmall-molecule EGFR TKI (first generation, reversible)
Erlotinib · Tarceva
Not mapped hereSmall-molecule EGFR TKI (first generation, reversible)
Gefitinib · Iressa
Not mapped hereNucleoside analogue (deoxycytidine)
Gemcitabine · Gemzar / Infugem
NegativeSmall molecule (claimed PARP inhibitor)
Iniparib
Phase 3Personalised mRNA neoantigen vaccine
Intismeran autogene
ApprovedMonoclonal antibody (anti-CTLA-4)
Ipilimumab · Yervoy
Under reviewBispecific antibody (PD-1×VEGF)
Ivonescimab
Phase 3Bispecific ADC
Izalontamab brengitecan
Not mapped hereSmall-molecule pan-TRK inhibitor (first generation)
Larotrectinib · Vitrakvi
ApprovedSmall-molecule kinase inhibitor (EGFR)
Lazertinib · Lazcluze
ApprovedTIL cell therapy
Lifileucel · Amtagvi
ApprovedSmall-molecule kinase inhibitor (ALK/ROS1)
Lorlatinib · Lorbrena
WithdrawnSmall-molecule EGFR exon 20 insertion TKI (irreversible)
Mobocertinib · Exkivity
Phase 3Small-molecule kinase inhibitor (ALK)
Neladalkib
ApprovedMonoclonal antibody (anti-PD-1)
Nivolumab · Opdivo / Opdivo Qvantig (SC)
Phase 3Small-molecule inhibitor (KRAS G12C)
Olomorasib
ApprovedDevice (tumour treating fields)
Optune / Optune Pax (TTFields) · Optune
ApprovedSmall-molecule kinase inhibitor (EGFR)
Osimertinib · Tagrisso
ApprovedCytotoxic chemotherapy (taxane)
Paclitaxel / nab-paclitaxel · Taxol / Abraxane
Not mapped hereFolate receptor-targeted near-infrared fluorescent imaging agent
Pafolacianine · Cytalux
Phase 3ADC
Patritumab deruxtecan
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
ApprovedCytotoxic (antifolate)
Pemetrexed · Alimta (and generics)
ApprovedSmall-molecule kinase inhibitor (RET)
Pralsetinib · Gavreto
ApprovedMonoclonal antibody (anti-VEGFR2)
Ramucirumab · Cyramza
ApprovedSmall-molecule kinase inhibitor (ROS1 / NTRK)
Repotrectinib · Augtyro
Under reviewADC
Sacituzumab tirumotecan
ApprovedSmall-molecule kinase inhibitor (RET)
Selpercatinib · Retevmo
ApprovedSmall-molecule kinase inhibitor (HER2)
Sevabertinib · Hyrnuo
EstablishedTumour-informed ctDNA MRD test
Signatera
ApprovedSmall-molecule inhibitor (KRAS G12C)
Sotorasib · Lumakras
Not mapped hereSmall-molecule EGFR exon 20 insertion TKI (irreversible)
Sunvozertinib · Zegfrovy
Not mapped hereSmall-molecule ROS1 TKI (next generation, CNS-penetrant)
Taletrectinib · Ibtrozi
ApprovedADC
Telisotuzumab vedotin · Emrelis
Phase 2Bispecific ADC
Tilatamig samrotecan
NegativeMonoclonal antibody (anti-TIGIT)
Tiragolumab
ApprovedMonoclonal antibody (anti-PD-1)
Tislelizumab · Tevimbra
ApprovedADC
Trastuzumab deruxtecan · Enhertu
Not mapped hereADC
Trastuzumab rezetecan
ApprovedMonoclonal antibody (anti-CTLA-4)
Tremelimumab · Imjudo
WithdrawnADC
Tusamitamab ravtansine
Not mapped hereSemi-synthetic vinca alkaloid
Vinorelbine · Navelbine
ApprovedBispecific antibody (HER2×HER3)
Zenocutuzumab · Bizengri
ApprovedSmall-molecule kinase inhibitor (ROS1)
Zidesamtinib · Jideytro
Phase 2Small-molecule RAS(ON) G12D-selective inhibitor
Zoldonrasib
ApprovedSmall-molecule kinase inhibitor (HER2)
Zongertinib · Hernexeos

companies

22
AbbVie (incl. ImmunoGen, Capstan)AkesoAmgenAstraZenecaBayerBoehringer IngelheimBristol Myers SquibbDaiichi SankyoDELFI DiagnosticsEli Lilly (incl. Loxo)Frontier MedicinesJiangsu Hengrui PharmaceuticalsJiangsu Hengrui PharmaceuticalsJohnson & JohnsonLunitMerck & Co. (MSD)NovartisNuvalentPfizer (incl. Seagen)Roche / GenentechSummit TherapeuticsTubulis (Gilead)

institutions

80
Aichi Cancer CenterApollo Hospitals (Apollo Cancer Centres)Auckland City Hospital / Te Pūriri o Te Ora Cancer and Blood ServiceBarts Cancer Institute / Barts Health NHS TrustCancer Center Clínica Universidad de Navarra / CIMACancer Council AustraliaCancer Grand ChallengesCancer Research UK Manchester InstituteCentre hospitalier de l'Université de Montréal (CHUM)Centro Nacional de Investigaciones Oncológicas (CNIO)Chang Gung Memorial HospitalChinese Society of Clinical OncologyDana-Farber Brigham Cancer CenterErasmus MC Cancer InstituteETOP IBCSG Partners FoundationGuangdong Provincial People's HospitalHarold C. Simmons Comprehensive Cancer Center, UT SouthwesternHealthCare Global EnterprisesHenan Cancer HospitalHokkaido University HospitalHospital Universitario 12 de OctubreHunan Cancer HospitalInselspital, Bern University Hospital / University Cancer Center InselspitalInstituto Alexander FlemingInstituto Nacional de Câncer (INCA)Instituto Nacional de Cancerología (Mexico)Intergroupe Francophone de Cancérologie ThoraciqueInternational Association for the Study of Lung CancerIRCCS Azienda Ospedaliero-Universitaria di Bologna – Policlinico Sant'OrsolaIRCCS Humanitas Research HospitalIRCCS Regina Elena National Cancer InstituteIstanbul University Institute of OncologyIstituto Nazionale Tumori IRCCS Fondazione G. PascaleJapan Clinical Oncology Group (JCOG)King Hussein Cancer CenterKoo Foundation Sun Yat-Sen Cancer CenterKorean Cancer Study GroupKyoto University HospitalKyushu University HospitalLaura and Isaac Perlmutter Cancer Center at NYU Langone HealthLausanne University Hospital (CHUV) / Ludwig Institute LausanneMaria Skłodowska-Curie National Research Institute of OncologyMarkey Cancer Center, University of KentuckyMUSC Hollings Cancer CenterNational Cancer Center Hospital EastNational Cancer Center KoreaNational Cancer Centre SingaporeNational Taiwan University HospitalNational University Hospital / National University Cancer Institute, SingaporeOsaka International Cancer InstitutePrince of Wales Hospital / Chinese University of Hong KongQueen Mary Hospital / University of Hong KongRajiv Gandhi Cancer Institute and Research CentreRigshospitalet – Copenhagen University HospitalSeoul National University HospitalShandong Cancer Hospital and InstituteShanghai Chest HospitalShanghai Pulmonary HospitalShizuoka Cancer CenterStand Up To CancerTaipei Veterans General HospitalThe Francis Crick InstituteTohoku University HospitalTROG Cancer ResearchUC Davis Comprehensive Cancer CenterUniklinik Köln (CIO)Union Hospital, Tongji Medical CollegeUniversity College London Hospitals / UCL Cancer InstituteUniversity Hospital Basel / Tumour CentreUniversity Hospital Southampton / Centre for Cancer ImmunologyUniversity Hospital Zurich / Comprehensive Cancer Center ZurichUniversity of Colorado Cancer CenterUniversity of Hawai'i Cancer CenterVanderbilt-Ingram Cancer CenterVCU Massey Comprehensive Cancer CenterVelindre Cancer CentreVietnam National Cancer Hospital (K Hospital)West Japan Oncology GroupWinship Cancer Institute of Emory UniversityZhejiang Cancer Hospital

pathways

12
Cancer cachexiaEpithelial–mesenchymal transition & drug effluxField cancerisationKEAP1–NRF2 antioxidant pathwayLineage plasticity & neuroendocrine transformationPD-1 / PD-L1 immune checkpoint & T-cell activationPI3K / AKT / mTORRAS / RAF / MEK / ERK (MAPK)Receptor tyrosine kinase activationSWI/SNF chromatin remodellingThe blood–brain barrier & brain metastasisVEGF angiogenesis

terms

33
AdenocarcinomaAdenocarcinomaBRAF V600E mutationBrain metastases (intracranial disease)Bronchoscopy (EBUS, robotic navigation)Cancer cachexiaChemoradiation (chemoradiotherapy, CRT)Consolidation therapyDifferentiationEGFR C797SEGFR exon 19 deletion & L858REGFR exon 20 insertionEGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M)HER2-positive (IHC 3+ or ISH-amplified)Histologic transformationKRAS mutation subtypes (G12C, G12D, G12V)LobectomyMaintenance therapyMaintenance therapyMalignant pleural effusion and ascitesMediastinumMET amplification (bypass resistance)OligoprogressionPleuraPleurodesis and indwelling pleural catheterPneumonectomyResectable, borderline resectable and unresectableSegmentectomy (sublobar resection)Squamous cell carcinomaSquamous cell carcinoma (SCC)STK11 / KEAP1 co-mutationsTumour proportion score (TPS)Tumour-agnostic (tissue-agnostic) approval

trials

26
ADAURAALINAALKOVE-1CheckMate 816CodeBreaK 200CROWNFLAURA2HARMONi-2HARMONi-3HERTHENA-Lung02KEYNOTE-024 & KEYNOTE-189KEYNOTE-671Krascendo 1KRYSTAL-12LAURALIBRETTO-431Low-dose olanzapine for cancer anorexia (Tata Memorial)MARIPOSANLST & NELSON (low-dose CT screening)PACIFICPonsegromab phase 2 in cancer cachexiaROMANA 1 and ROMANA 2SOHO-01TeliMET NSCLC-01TROPION-Lung01TROPION-Lung05

pairings

10
ADC + checkpoint inhibitorAmivantamab + lazertinib (first-line EGFR NSCLC)BRAF inhibitor + MEK inhibitorCaution: TIGIT + PD-(L)1 blockadeEGFR TKI → ADC on progressionPD-1 blockade + chemotherapy in PD-L1-low NSCLCPD-1 blockade + VEGF inhibitionRadiotherapy + immunotherapySequence: targeted therapy before immunotherapy in driver-positive NSCLCTROP2 PET → TROP2 ADC selection

roadmaps

4
ADC roadmap: from Mylotarg to bispecific and dual-payload ADCsImmunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunityKRAS roadmap: undruggable → G12C → pan-RASTROP2 ADC roadmap: sacituzumab govitecan → Dato-DXd → sac-TMT → bispecifics and PET

ideas

83
A cheap old tablet to restore appetiteA clone report from blood at every treatment cycleA coordinated FLASH radiotherapy evidence programme with shared dose-rate standardsA delivery-science moonshot for prevention we already ownA standard platform to get drugs into the brain: focused ultrasound plus shuttle-engineered therapeuticsA standing platform for testing new drugs with radiotherapyA test to tell true oligometastatic disease from hidden widespread spreadAdd a drug when the blood test turns, without stopping the one that worksAdd the second drug on day one when the escape route is predictableAI clears the normal lung screening scans so radiologists read only the suspicious onesAI malignancy scores to end repeat scans and biopsies for benign lung nodulesAutomatic palliative care referral triggered by diagnosis, not by declineAutonomous closed-loop adaptive therapy driven by blood tests and evolutionary modelsBank three spatially separate tumour blocks from every resectionBiopsy the one lesion that is growing while the others shrinkBlock the complement signal that recruits tumour-protecting cellsBlunt the inflammation that wakes sleeping cancer cellsBorrow from past control arms to shrink the control group in phase 3Brain metastases included by default in every solid-tumour trialBuild a human model of the barrier that guards the brain fluidBurden-weighted portfolio targets for every major cancer funderCapture diet, fibre and antibiotic exposure in every immunotherapy pivotal trialCatch wasting early with a smart scale and a step counterCD8 PET to stop or switch immunotherapy earlyCombine the new anti-wasting antibody with exercise and proteinCompeting sponsors share one control arm in the same indicationConfirm low-dose olanzapine for appetite and weight in advanced cancer worldwideConfirm or refute the harm of antioxidant supplements during chemotherapyConfirm ultra-low-dose immunotherapy so it can be afforded where most patients livectDNA-guided dose holidays for lung cancer targeted therapyDedicated cohorts for patients with performance status 2 in first-line trialsDetect tumours changing cell type from RNA in the bloodEvaluate clean-air policies using lung cancer in never-smokersEvery lung screening visit includes stop-smoking medicine, opt-outEvery routine CT scan checked by AI for early cancer signs, with a tracked follow-up pathwayExtended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stableGet the one approved appetite drug licensed beyond a single countryGive immunotherapy in the morningIntercept cancer at the field stageKill drug-tolerant persisters through ferroptosisLook for the resistant sub-population before the first doseLung screening eligibility by risk score, not pack-years, including high-risk never-smokersMake bespoke mouse cancer models in weeks with in vivo gene editingMake cigarettes non-addictive by capping their nicotineMandatory radon testing when homes are sold, with subsidised mitigationMap metabolic dependencies in the patient, not the dishMicrobiome transplant as a routine immunotherapy adjunctMolecular indolence classifiers bundled with every screening programmePathologists order genomic profiling automatically at diagnosis of advanced cancerPause a failed drug so the tumour becomes sensitive to it againPre-surgery platform trials that test combinations on pathological response in monthsPrevention trials aimed only at brain metastasisProtect hearing from cisplatin in adults as we now do in childrenProtect the gut flora of patients about to start immunotherapyPut cytisine, a cheap plant-based quit-smoking pill, on every essential medicines listRandomise a cheap antihistamine alongside immunotherapyRandomised trials of stopping immunotherapy after one year versus continuingRe-test the metastasis, not the old primary, before every change of treatmentSelect cachexia trial patients by the hormone driving their wastingSelect patients for cell therapy by whether their tumour holds reactive T cellsSlow the tumour's mutation engine with APOBEC inhibitors during targeted therapySmoke-free generation laws with a built-in evaluation across countriesSocial impact bonds for cancer prevention, repaid from avoided treatment costsStanding reflex biomarker panels per tumour type, run without an oncologist's orderSwitch drugs at maximum response, not at relapseTake lung screening scanners to supermarket car parks in the poorest areasTest a high-fibre diet as an immunotherapy adjunctTest alternating drug schedules against giving both drugs at onceTest intermittent dosing of targeted drugs to delay resistance, with honest priorsTest protein and resistance training during immunotherapyTreat brain metastases as a disease with its own trials programmeTreat cachexia as a disease: GDF-15 blockade plus anabolic and nutrition bundlesTreat cachexia before it startsTreat immunotherapy side-effects without wiping out the responseTROP2 PET to choose and sequence TROP2 ADCsTurn a brake back on: drugs that reactivate the PP2A phosphataseUnmask hidden antigens with a short epigenetic course before immunotherapyUse a blood test at six weeks to decide whether to keep goingUse a hypoxia scan to pick patients for adenosine-pathway drugsUse the brain's own transport door to carry antibody drugs acrossUse tumour DNA in blood to decide when to pause treatment in metastatic cancerVideo palliative care as an equivalent default option for patients far from a teamWatch the immune system's response in the blood three weeks in

collections

1
LUNGevity Foundation (and GO2 for Lung Cancer)

people

67
Alexander DrilonAnne C. ChiangAsh A. AlizadehBenjamin BesseBenjamin SolomonBob T. LiByoung Chul ChoCaicun ZhouCharles SwantonCharu AggarwalDae Ho LeeDaniel A. HaberDong-Wan KimDongsheng TuEnriqueta FelipEric B. HauraEverett E. VokesFabrice BarlesiFiona BlackhallFrank McCormickHaruhiko FukudaHeather A. WakeleeHelena A. YuHye Ryun KimJean-Charles SoriaJie HeJie WangJohn V. HeymachJulie R. BrahmerJürgen WolfJustin F. GainorKathy S. AlbainKevan M. ShokatKoichi GotoKumar PrabhashLecia V. SequistLi ZhangMatthew MeyersonMaximilian DiehnMiriam MeradMyung-Ju AhnNatasha B. LeighlNathan A. PennellPasi A. JännePatrick M. FordePilar GarridoPrimo N. Lara Jr.Ramaswamy GovindanReinhard BüttnerRoman ThomasSe-Hoon LeeShun LuSolange PetersStephen B. BaylinSuzanne L. TopalianTakashi KohnoTasuku HonjoThomas J. Lynch Jr.Timothy A. ChanVanita NoronhaWeimin LiWenfeng FangWoong-Yang ParkYi-Long WuYou LuYuankai ShiYuichiro Ohe

bottlenecks

23
Acquired resistance to every therapyAI that is built but not validated or deployedBiomarkers are not validated or standardisedCachexia, toxicity and the limits of the patientDormant cells and minimal residual diseaseFragmented care and guideline gapsFunding follows fashion, not burdenIncentives reward me-too drugs and marginal gainsKnowledge reaches practice too slowlyMetastasis is understood least and studied lastMisinformation and unproven therapiesMost lethal cancers are found lateNo one can predict who responds to immunotherapyOlder and multimorbid patients are excluded and undertreatedOverdiagnosis and false alarmsPain relief and palliative care are unavailable to mostPrevention we already have is not deployedThe brain: barrier and sanctuaryThe undruggable driversToo many combinations to testTrials do not represent the people who get cancerTumour heterogeneity and clonal evolutionWrong doses

key papers

19
ADAURA: three years of osimertinib after surgery for EGFR-mutated lung cancerASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitorsCheckMate 816: three cycles of nivolumab plus chemotherapy before lung cancer surgeryCodeBreaK 200: sotorasib versus docetaxel in KRAS G12C-mutated lung cancer, a modest win for the first KRAS drugCROWN: lorlatinib versus crizotinib as first treatment for ALK-positive lung cancerDoll and Hill 1950: the case-control study that tied smoking to lung cancerFifty years of the British Doctors Study: smokers lose ten years of life, quitting gives most of it backFLAURA: osimertinib as first treatment for EGFR-mutated lung cancerHARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancerKEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutationMARIPOSA: amivantamab plus lazertinib versus osimertinib as first treatment for EGFR-mutated lung cancerNELSON: volume-based CT screening reduces lung cancer deaths with fewer false alarmsNLST: yearly low-dose CT scans cut lung cancer deaths in heavy smokersOstrem and Shokat: the hidden pocket that made KRAS G12C druggablePACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancerTemel: early palliative care alongside chemotherapy improved quality of life, mood and survival in lung cancerTopalian 2012: the first large trial of a PD-1 antibody shows durable responses across melanoma, lung and kidney cancerTRACERx 421: the full-cohort picture of how lung cancer evolves and which subclones drive relapseTRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse

journals

1
Journal of Thoracic Oncology