OnCo
cancersCancer

Small-cell lung cancer

A fast-growing lung cancer that responds to chemotherapy then relapses quickly. After 30 years without progress, T-cell engagers and ADCs are finally moving the needle.

Small-cell lung cancer is a high-grade neuroendocrine carcinoma, almost always caused by smoking, defined by near-universal loss of TP53 and RB1 and by explosive growth. It presents as extensive-stage disease in two thirds of patients, responds to chemotherapy in most, and relapses in almost all. For three decades the treatment was platinum-etoposide, thoracic radiotherapy for limited-stage disease, prophylactic cranial irradiation, and topotecan at relapse.

The field moved in three steps. First-line chemo-immunotherapy (IMpower133 2018, CASPIAN 2019, ASTRUM-005 2022) added two to five months of median survival and a small tail of long-term survivors. Consolidation durvalumab after chemoradiotherapy for limited-stage disease (ADRIATIC, approved December 2024) was the first curative-intent advance in 30 years, lifting median survival to nearly five years. In relapsed disease, tarlatamab, the DLL3 T-cell engager, became the first drug to beat chemotherapy on overall survival (DeLLphi-304; full FDA approval November 2025), and lurbinectedin plus atezolizumab became the first approved first-line maintenance regimen (IMforte, October 2025).

What is next: maintenance intensification with tarlatamab (DeLLphi-305), the B7-H3 ADC ifinatamab deruxtecan in second line (IDeate-Lung02), alpha-emitting SSTR radioligands (RYZ101), subtype-directed therapy (ASCL1, NEUROD1, POU2F3, inflamed), bispecific and trispecific DLL3 engagers, and the settled question of whether MRI surveillance can replace prophylactic cranial irradiation. Screening remains limited to low-dose CT in smokers, which detects few small-cell cancers early.

State of the art today

  • Tarlatamab: first OS improvement in relapsed SCLC in decades.
  • Immunotherapy consolidation in limited stage.
  • Extensive-stage first line: chemo-immunotherapy, now with lurbinectedin-atezolizumab maintenance (IMforte, 2025).
  • Relapse: tarlatamab (DLL3×CD3) improved OS over chemotherapy (DeLLphi-304) and received full approval in November 2025.
  • B7-H3 ADC ifinatamab deruxtecan and alpha-emitting SSTR radioligand RYZ101 are in phase 3.
  • MRI surveillance is displacing prophylactic cranial irradiation while the definitive trial (SWOG S1827) reads out.
  • Molecular subtypes (A/N/P/I) explain heterogeneity and are moving toward prospective use.
Show survival figures (1)

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.

  • Limited-stage: chemoradiation followed by durvalumab consolidation (ADRIATIC), median OS approaching five years.
Who it affects

Small-cell lung cancer makes up about 15% of lung cancers, roughly 250,000 cases a year worldwide, almost entirely in current or former smokers.

Show survival figures (1)

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.

  • Median survival is about one year in extensive-stage disease.
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. SCLC is roughly 15% of lung cancer; figures are for all lung cancer.

Standard of care

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Limited stage

Chemoradiation → durvalumab; prophylactic cranial irradiation or MRI surveillance.

NCCN Guidelines: Small Cell Lung Cancer
DurvalumabIMRT / IGRT (modern external beam)
Extensive stage

Platinum-etoposide + atezolizumab/durvalumab; lurbinectedin + atezolizumab maintenance.

NCCN Guidelines: Small Cell Lung Cancer
AtezolizumabDurvalumab
Relapsed

Tarlatamab (preferred), lurbinectedin, topotecan; I-DXd in trials.

NCCN Guidelines: Small Cell Lung Cancer
TarlatamabDeLLphi-304Ifinatamab deruxtecan
Screening and diagnosis

Low-dose CT screening in heavy smokers finds some SCLC but stage shift is limited; diagnosis by bronchoscopic or CT-guided biopsy; staging with PET/CT and brain MRI.

NCCN · SCLC guideline, staging workup
CT (computed tomography)PET/CTMRI
Very limited stage (T1-2 N0, ~5%)

Lobectomy with mediastinal node dissection or SBRT, followed by adjuvant platinum-etoposide; PCI or MRI surveillance.

NCCN · 2A
SBRT / SABR (stereotactic radiotherapy)Platinum + etoposide (EP / CE)Prophylactic cranial irradiation vs MRI surveillance
Limited stage

Concurrent cisplatin-etoposide with thoracic radiotherapy (45 Gy twice daily or 60-70 Gy once daily), then durvalumab consolidation up to 2 years (ADRIATIC); PCI or MRI surveillance.

NCCN · 1 (durvalumab consolidation, category 1)ESMO-MCBS · A
Platinum + etoposide (EP / CE)IMRT / IGRT (modern external beam)DurvalumabADRIATICCONVERTProphylactic cranial irradiation vs MRI surveillance
Extensive stage, first line

Carboplatin-etoposide plus atezolizumab or durvalumab (4 cycles), then maintenance immunotherapy; lurbinectedin added to atezolizumab maintenance since 2025 (IMforte). Serplulimab-chemotherapy where approved. Consolidative thoracic radiotherapy for residual thoracic disease in good responders.

NCCN · 1 (chemo-IO); 2A (lurbinectedin maintenance)ESMO-MCBS · 3
Platinum + etoposide (EP / CE)AtezolizumabDurvalumabLurbinectedinIMpower133CASPIANIMforteSerplulimab
Relapsed, platinum-sensitive (≥90 days)

Tarlatamab (preferred, OS benefit); platinum-etoposide rechallenge; lurbinectedin; topotecan.

NCCN · 1 (tarlatamab)ESMO-MCBS · 4
TarlatamabDeLLphi-304LurbinectedinTopotecan
Relapsed, platinum-resistant (<90 days)

Tarlatamab; lurbinectedin; topotecan; clinical trials (I-DXd, RYZ101, DLL3 bispecifics).

NCCN · 1 (tarlatamab)
TarlatamabLurbinectedinTopotecanIfinatamab deruxtecanIDeate-Lung02Actinium-225 DOTATATE
Brain metastases

Whole-brain radiotherapy or, increasingly, stereotactic radiosurgery for limited numbers of lesions; PCI decisions individualised.

SBRT / SABR (stereotactic radiotherapy)Prophylactic cranial irradiation vs MRI surveillanceMRI
Transformed SCLC (from EGFR-mutant NSCLC)

Platinum-etoposide, often with continued EGFR TKI; immunotherapy benefit uncertain; trials.

Platinum + etoposide (EP / CE)Osimertinib

Subtypes & biomarkers

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Subtypes
Biomarkers clinicians test
  • DLL3 (not required for tarlatamab)
  • B7-H3
  • SCLC-A/N/P/I subtypes (research)
  • Stage (limited vs extensive) is the dominant decision
  • B7-H3 (I-DXd trials)
  • SSTR2 (RYZ101)
  • Transcription-factor subtype (ASCL1/NEUROD1/POU2F3/YAP1, research)
  • PD-L1 and TMB (not predictive in SCLC)
  • SLFN11 (chemotherapy/PARP sensitivity, research)
  • ctDNA (research)

Target prevalence in this cancer

Target / alterationPrevalenceSource
TP53
RB1 co-loss
>90%
Wikipedia
DLL3
80-85%
Wikipedia
B7-H3
60-70%
Wikipedia
Somatostatin receptor 2
30-50%
Wikipedia
PD-L1
15-20%
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. 1973VA Lung Study Group defines limited vs extensive stage
    Limited-stage vs extensive-stage (SCLC)
  2. 1980Platinum-etoposide becomes standard
  3. 1985Platinum-etoposide becomes the standard regimen
    Platinum + etoposide (EP / CE)
  4. 1992Meta-analysis: thoracic radiotherapy improves survival in limited-stage disease
    IMRT / IGRT (modern external beam)
  5. 1996Topotecan approved for relapsed disease
    Topotecan
  6. 1999Prophylactic cranial irradiation improves survival in complete responders
    Prophylactic cranial irradiation vs MRI surveillance
  7. 1999Twice-daily 45 Gy (Turrisi) sets the limited-stage radiotherapy standard
    IMRT / IGRT (modern external beam)
  8. 2017CONVERT: once-daily 66 Gy not superior to twice-daily 45 Gy
    CONVERT
  9. 2017Japanese trial: PCI gives no survival benefit in extensive-stage disease with MRI surveillance
    Prophylactic cranial irradiation vs MRI surveillance
  10. 2018IMpower133: first immunotherapy OS benefit
    Atezolizumab
  11. 2018IMpower133: first survival gain in decades with atezolizumab
    IMpower133Atezolizumab
  12. 2019Rovalpituzumab tesirine (first DLL3 ADC) fails
  13. 2019Rovalpituzumab tesirine (first DLL3 ADC) fails
    DLL3
  14. 2019CASPIAN confirms chemo-immunotherapy with durvalumab
    CASPIANDurvalumab
  15. 2020Lurbinectedin accelerated approval in relapsed SCLC
    Lurbinectedin
  16. 2021SCLC molecular subtypes (A, N, P, I) proposed
    Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)
  17. 2024Tarlatamab approved
    Tarlatamab
  18. 2024Tarlatamab accelerated approval; ADRIATIC changes limited-stage care
    TarlatamabADRIATIC
  19. 2025DeLLphi-304 OS benefit and full approval of tarlatamab; IMforte maintenance approved
    DeLLphi-304IMforteLurbinectedin
  20. 2026Phase 3 readouts pending for I-DXd and tarlatamab maintenance
    IDeate-Lung02DeLLphi-305

Pipeline

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Phase 3ADC
Ifinatamab deruxtecan
Phase 3Targeted alpha therapy
Actinium-225 DOTATATE
ApprovedBispecific T-cell engager (DLL3×CD3)
Tarlatamab · Imdelltra
Under reviewMonoclonal antibody (anti-PD-1)
Serplulimab · Hansizhuang / Hetronifly
ApprovedCytotoxic (transcription inhibitor)
Lurbinectedin · Zepzelca
DeLLphi-305IDeate-Lung02Subtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)MRI surveillance replaces prophylactic cranial irradiation in SCLCProphylactic cranial irradiation vs MRI surveillanceSequencing DLL3 engager and B7-H3 ADC in relapsed SCLCChemo-immunotherapy induction → maintenance intensification (SCLC)T-cell engagers (bispecific)Targeted alpha therapy

Open problems

  • Rapid chemoresistance.
  • Brain metastases.
  • No screening beyond CT for smokers.
  • Near-universal relapse after first-line therapy in extensive-stage disease; median survival still barely over a year.
  • No validated predictive biomarker for immunotherapy benefit; PD-L1 and TMB do not work in SCLC.
  • Sequencing of tarlatamab, I-DXd, lurbinectedin, and platinum rechallenge is untested.
  • Cytokine release syndrome and neurotoxicity of T-cell engagers require inpatient step-up dosing that many community centres cannot provide.
  • Prophylactic cranial irradiation versus MRI surveillance remains unresolved until SWOG S1827 reads out.
  • Transformed SCLC arising from EGFR-mutant NSCLC has no dedicated evidence base.
  • Screening rarely catches SCLC early; prevention is tobacco control.
  • Trials rarely enrol patients with poor performance status, who are common in this disease.

Trials

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Recruiting now (live from ClinicalTrials.gov)

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

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Landmark trials in OnCo

ADRIATICASTRUM-005ATLANTISCASPIANCONVERTDeLLphi-304DeLLphi-305IDeate-Lung02IMforteIMpower133

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 Small-cell lung cancer

Generated from this cancer's standard of care, biomarkers, and pipeline · 34 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 DLL3, B7-H3, SCLC-A/N/P/I subtypes, Stageis the dominant decision, B7-H3), 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 Limited-stage, Extensive-stage, SCLC-A.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Limited stage

  1. For my situation (limited stage), which of the standard options do you recommend and why?
    Why: Guideline options include: Chemoradiation → durvalumab; prophylactic cranial irradiation or MRI surveillance.
  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 (limited stage), which of the standard options do you recommend and why?
    Why: Guideline options include: Concurrent cisplatin-etoposide with thoracic radiotherapy (45 Gy twice daily or 60-70 Gy once daily), then durvalumab consolidation up to 2 years (ADRIATIC); PCI or MRI surveillance.
  4. Am I a candidate for Platinum + etoposide (EP / CE), Durvalumab, 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 ADRIATIC and CONVERT apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Extensive stage

  1. For my situation (extensive stage), which of the standard options do you recommend and why?
    Why: Guideline options include: Platinum-etoposide + atezolizumab/durvalumab; lurbinectedin + atezolizumab maintenance.
  2. Am I a candidate for Atezolizumab, Durvalumab, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Relapsed

  1. For my situation (relapsed), which of the standard options do you recommend and why?
    Why: Guideline options include: Tarlatamab (preferred), lurbinectedin, topotecan; I-DXd in trials.
  2. Am I a candidate for Tarlatamab, Ifinatamab 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 DeLLphi-304 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Screening and diagnosis

  1. For my situation (screening and diagnosis), which of the standard options do you recommend and why?
    Why: Guideline options include: Low-dose CT screening in heavy smokers finds some SCLC but stage shift is limited; diagnosis by bronchoscopic or CT-guided biopsy; staging with PET/CT and brain MRI.

Very limited stage (T1-2 N0, ~5%)

  1. For my situation (very limited stage (t1-2 n0, ~5%)), which of the standard options do you recommend and why?
    Why: Guideline options include: Lobectomy with mediastinal node dissection or SBRT, followed by adjuvant platinum-etoposide; PCI or MRI surveillance.
  2. Am I a candidate for Platinum + etoposide (EP / CE), and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Extensive stage, first line

  1. For my situation (extensive stage, first line), which of the standard options do you recommend and why?
    Why: Guideline options include: Carboplatin-etoposide plus atezolizumab or durvalumab (4 cycles), then maintenance immunotherapy; lurbinectedin added to atezolizumab maintenance since 2025 (IMforte). Serplulimab-chemotherapy where approved. Consolidative thoracic radiotherapy for residual thoracic disease in good responders.
  2. Am I a candidate for Platinum + etoposide (EP / CE), Atezolizumab, Durvalumab 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 IMpower133 and CASPIAN apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Relapsed, platinum-sensitive (≥90 days)

  1. For my situation (relapsed, platinum-sensitive (≥90 days)), which of the standard options do you recommend and why?
    Why: Guideline options include: Tarlatamab (preferred, OS benefit); platinum-etoposide rechallenge; lurbinectedin; topotecan.
  2. Am I a candidate for Tarlatamab, Lurbinectedin, Topotecan, 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 DeLLphi-304 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Relapsed, platinum-resistant (<90 days)

  1. For my situation (relapsed, platinum-resistant (<90 days)), which of the standard options do you recommend and why?
    Why: Guideline options include: Tarlatamab; lurbinectedin; topotecan; clinical trials (I-DXd, RYZ101, DLL3 bispecifics).
  2. Am I a candidate for Tarlatamab, Lurbinectedin, Topotecan 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 IDeate-Lung02 apply to someone like me?
    Why: Trial populations differ from individual patients; ask how closely you match.

Brain metastases

  1. For my situation (brain metastases), which of the standard options do you recommend and why?
    Why: Guideline options include: Whole-brain radiotherapy or, increasingly, stereotactic radiosurgery for limited numbers of lesions; PCI decisions individualised.

Transformed SCLC (from EGFR-mutant NSCLC)

  1. For my situation (transformed sclc (from egfr-mutant nsclc)), which of the standard options do you recommend and why?
    Why: Guideline options include: Platinum-etoposide, often with continued EGFR TKI; immunotherapy benefit uncertain; trials.
  2. Am I a candidate for Platinum + etoposide (EP / CE), Osimertinib, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Any stage

  1. Are there clinical trials I could join, for example of Ifinatamab deruxtecan, Actinium-225 DOTATATE, Tarlatamab, DeLLphi-305?
    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 “Rapid chemoresistance”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “Brain metastases”. 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

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

technologies

19
Antibody-drug conjugate (ADC)Autologous stem cell transplant (high-dose therapy)CT (computed tomography)Cytotoxic chemotherapyImmune checkpoint inhibitorsIMRT / IGRT (modern external beam)Low-dose CT lung screeningMRD / molecular residual disease testingMRIPET/CTPlatinum agentsProphylactic cranial irradiation vs MRI surveillanceSBRT / SABR (stereotactic radiotherapy)Small-molecule kinase inhibitorsSmoking cessation in cancer patientsSomatostatin receptor PET (68Ga/64Cu-DOTATATE)T-cell engagers (bispecific)Targeted alpha therapyTopoisomerase-I inhibitors (and ADC payloads)

targets

13
ATRB7-H3BCL-2CD3DLL3EGFRKMT2A (MLL) rearrangementPARPPD-1PD-L1Somatostatin receptor 2TIGITTP53

drugs

15
Phase 3Targeted alpha therapy
Actinium-225 DOTATATE
ApprovedMonoclonal antibody (anti-PD-L1)
Atezolizumab · Tecentriq / Tecentriq Hybreza (SC)
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
ApprovedMonoclonal antibody (anti-PD-L1)
Durvalumab · Imfinzi
Not mapped hereTopoisomerase II inhibitor (podophyllotoxin derivative)
Etoposide · VePesid / Etopophos / Toposar
Phase 3ADC
Ifinatamab deruxtecan
Not mapped hereTopoisomerase I inhibitor (camptothecin prodrug)
Irinotecan (and liposomal irinotecan) · Camptosar / Onivyde
ApprovedCytotoxic (transcription inhibitor)
Lurbinectedin · Zepzelca
ApprovedSmall-molecule kinase inhibitor (EGFR)
Osimertinib · Tagrisso
Not mapped hereCytotoxic regimen
Platinum + etoposide (EP / CE)
WithdrawnADC
Rovalpituzumab tesirine
Under reviewMonoclonal antibody (anti-PD-1)
Serplulimab · Hansizhuang / Hetronifly
ApprovedBispecific T-cell engager (DLL3×CD3)
Tarlatamab · Imdelltra
NegativeMonoclonal antibody (anti-TIGIT)
Tiragolumab
ApprovedCytotoxic (topoisomerase-I inhibitor)
Topotecan · Hycamtin

companies

16
AbbVie (incl. ImmunoGen, Capstan)Aktis OncologyAmgenAstraZenecaBristol Myers SquibbCircle PharmaDaiichi SankyoDebiopharmIpsenJazz PharmaceuticalsMerck & Co. (MSD)Pfizer (incl. Seagen)PharmaMarRayzeBio (BMS)Roche / GenentechShanghai Henlius Biotech

institutions

12
Cancer Research UK Manchester InstituteDana-Farber Brigham Cancer CenterGustave RoussyHospital Universitario 12 de OctubreIntergroupe Francophone de Cancérologie ThoraciqueInternational Association for the Study of Lung CancerMD Anderson Cancer CenterMemorial Sloan Kettering Cancer CenterShandong Cancer Hospital and InstituteShanghai Chest HospitalShanghai Pulmonary HospitalWest Japan Oncology Group

pathways

7
Intrinsic apoptosis (BCL-2 family)Lineage plasticity & neuroendocrine transformationNotch signallingp53 / RB / cell-cycle checkpointPD-1 / PD-L1 immune checkpoint & T-cell activationThe blood–brain barrier & brain metastasisThe cell-cycle engine (cyclins & CDKs)

terms

12
Bronchoscopy (EBUS, robotic navigation)Consolidation therapyCytokine release syndrome (CRS)DifferentiationHistologic transformationLimited-stage vs extensive-stage (SCLC)Limited-stage vs extensive-stage (small-cell lung cancer)Neuroendocrine tumour grade (Ki-67) and WHO classificationOverall survival (OS)Platinum-sensitive / platinum-resistantProgression-free survival (PFS)Prophylactic cranial irradiation (PCI)

trials

10
ADRIATICASTRUM-005ATLANTISCASPIANCONVERTDeLLphi-304DeLLphi-305IDeate-Lung02IMforteIMpower133

pairings

4
Caution: TIGIT + PD-(L)1 blockadeChemo-immunotherapy induction → maintenance intensification (SCLC)Radiotherapy + immunotherapySequencing DLL3 engager and B7-H3 ADC in relapsed SCLC

ideas

7
Detect tumours changing cell type from RNA in the bloodGrow blood-borne tumour cells to test drugs on the cells that actually spreadGrow models from tumour cells in the blood when a biopsy is impossibleMRI surveillance replaces prophylactic cranial irradiation in SCLCmRNA-delivered MYC decoy proteins instead of MYC inhibitorsStarve MYC-driven tumours by blocking protein production machinerySubtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)

collections

1
LUNGevity Foundation (and GO2 for Lung Cancer)

people

8
Anne C. ChiangCaroline DiveFiona BlackhallJie WangJohn V. HeymachRoman ThomasSe-Hoon LeeYuichiro Ohe

bottlenecks

1
The brain: barrier and sanctuary

key papers

5
ADRIATIC: durvalumab after chemoradiotherapy for limited-stage small-cell lung cancerDeLLphi-301: tarlatamab, a DLL3-targeting T-cell engager, in previously treated small-cell 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 backNLST: yearly low-dose CT scans cut lung cancer deaths in heavy smokers

Key papers

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rctNew England Journal of Medicine 2024changed practice
ADRIATIC: durvalumab after chemoradiotherapy for limited-stage small-cell lung cancer

Patients with limited-stage small-cell lung cancer who complete chemoradiotherapy without progression should now be offered up to two years of durvalumab consolidation, which extends life by almost two years on average. This is the first survival improvement for limited-stage disease since twice-daily radiotherapy and prophylactic cranial irradiation, and small-cell lung cancer is no longer a disease where immunotherapy gives only marginal gains.

rctNew England Journal of Medicine 2023changed practice
DeLLphi-301: tarlatamab, a DLL3-targeting T-cell engager, in previously treated small-cell lung cancer

Patients with small-cell lung cancer that has relapsed after chemotherapy now have a drug that works far better than topotecan or lurbinectedin, and it is the first T-cell engager approved for a solid tumour. Treatment requires inpatient monitoring for the first doses because of cytokine release syndrome, which most centres now manage on a short-stay basis. It does not yet apply to first-line treatment, where trials are ongoing.

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.

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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Literature trend8,054 papers in the last 12 months+7% vs prior 12How this is computed
Latest papers · live from Europe PMC
Open in Europe PMC

Query for this cancer: (TITLE:"Small-cell lung cancer" OR ABSTRACT:"Small-cell lung cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Small-cell lung cancer, not a curated reading list.

Connected

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Pages like this

not linked directly; found by shared links

technologies

14
Antibody-drug conjugate (ADC)CT (computed tomography)Cytotoxic chemotherapyImmune checkpoint inhibitorsIMRT / IGRT (modern external beam)Low-dose CT lung screeningMRIPET/CTProphylactic cranial irradiation vs MRI surveillanceSBRT / SABR (stereotactic radiotherapy)Smoking cessation in cancer patientsSomatostatin receptor PET (68Ga/64Cu-DOTATATE)T-cell engagers (bispecific)Targeted alpha therapy

targets

10
ATRB7-H3BCL-2DLL3PARPPD-1PD-L1Somatostatin receptor 2TIGITTP53

drugs

15
Phase 3Targeted alpha therapy
Actinium-225 DOTATATE
ApprovedMonoclonal antibody (anti-PD-L1)
Atezolizumab · Tecentriq / Tecentriq Hybreza (SC)
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
ApprovedMonoclonal antibody (anti-PD-L1)
Durvalumab · Imfinzi
Not mapped hereTopoisomerase II inhibitor (podophyllotoxin derivative)
Etoposide · VePesid / Etopophos / Toposar
Phase 3ADC
Ifinatamab deruxtecan
Not mapped hereTopoisomerase I inhibitor (camptothecin prodrug)
Irinotecan (and liposomal irinotecan) · Camptosar / Onivyde
ApprovedCytotoxic (transcription inhibitor)
Lurbinectedin · Zepzelca
ApprovedSmall-molecule kinase inhibitor (EGFR)
Osimertinib · Tagrisso
Not mapped hereCytotoxic regimen
Platinum + etoposide (EP / CE)
WithdrawnADC
Rovalpituzumab tesirine
Under reviewMonoclonal antibody (anti-PD-1)
Serplulimab · Hansizhuang / Hetronifly
ApprovedBispecific T-cell engager (DLL3×CD3)
Tarlatamab · Imdelltra
NegativeMonoclonal antibody (anti-TIGIT)
Tiragolumab
ApprovedCytotoxic (topoisomerase-I inhibitor)
Topotecan · Hycamtin

companies

12
Aktis OncologyAmgenAstraZenecaBristol Myers SquibbCircle PharmaDaiichi SankyoDebiopharmJazz PharmaceuticalsMerck & Co. (MSD)PharmaMarRoche / GenentechShanghai Henlius Biotech

institutions

12
Cancer Research UK Manchester InstituteDana-Farber Brigham Cancer CenterGustave RoussyHospital Universitario 12 de OctubreIntergroupe Francophone de Cancérologie ThoraciqueInternational Association for the Study of Lung CancerMD Anderson Cancer CenterMemorial Sloan Kettering Cancer CenterShandong Cancer Hospital and InstituteShanghai Chest HospitalShanghai Pulmonary HospitalWest Japan Oncology Group

pathways

7
Intrinsic apoptosis (BCL-2 family)Lineage plasticity & neuroendocrine transformationNotch signallingp53 / RB / cell-cycle checkpointPD-1 / PD-L1 immune checkpoint & T-cell activationThe blood–brain barrier & brain metastasisThe cell-cycle engine (cyclins & CDKs)

terms

12
Bronchoscopy (EBUS, robotic navigation)Consolidation therapyCytokine release syndrome (CRS)DifferentiationHistologic transformationLimited-stage vs extensive-stage (SCLC)Limited-stage vs extensive-stage (small-cell lung cancer)Neuroendocrine tumour grade (Ki-67) and WHO classificationOverall survival (OS)Platinum-sensitive / platinum-resistantProgression-free survival (PFS)Prophylactic cranial irradiation (PCI)

trials

10
ADRIATICASTRUM-005ATLANTISCASPIANCONVERTDeLLphi-304DeLLphi-305IDeate-Lung02IMforteIMpower133

pairings

4
Caution: TIGIT + PD-(L)1 blockadeChemo-immunotherapy induction → maintenance intensification (SCLC)Radiotherapy + immunotherapySequencing DLL3 engager and B7-H3 ADC in relapsed SCLC

ideas

7
Detect tumours changing cell type from RNA in the bloodGrow blood-borne tumour cells to test drugs on the cells that actually spreadGrow models from tumour cells in the blood when a biopsy is impossibleMRI surveillance replaces prophylactic cranial irradiation in SCLCmRNA-delivered MYC decoy proteins instead of MYC inhibitorsStarve MYC-driven tumours by blocking protein production machinerySubtype-directed therapy for SCLC (ASCL1 / NEUROD1 / POU2F3 / inflamed)

collections

1
LUNGevity Foundation (and GO2 for Lung Cancer)

people

8
Anne C. ChiangCaroline DiveFiona BlackhallJie WangJohn V. HeymachRoman ThomasSe-Hoon LeeYuichiro Ohe

bottlenecks

1
The brain: barrier and sanctuary

key papers

5
ADRIATIC: durvalumab after chemoradiotherapy for limited-stage small-cell lung cancerDeLLphi-301: tarlatamab, a DLL3-targeting T-cell engager, in previously treated small-cell 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 backNLST: yearly low-dose CT scans cut lung cancer deaths in heavy smokers