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Salivary gland cancers

aka Adenoid cystic carcinoma, Mucoepidermoid carcinoma, Salivary duct carcinoma, Secretory carcinoma

Salivary gland cancers are a family of over 20 rare cancers, each with its own behaviour and often its own gene fusion. Surgery and radiation treat most; drug therapy is now chosen by the specific subtype, from anti-HER2 or anti-androgen drugs to NTRK inhibitors.

Salivary gland carcinomas are defined increasingly by fusion genes: MYB-NFIB in adenoid cystic carcinoma (ACC), CRTC1-MAML2 in mucoepidermoid carcinoma, ETV6-NTRK3 in secretory carcinoma, PLAG1/HMGA2 fusions in carcinoma ex pleomorphic adenoma, and androgen receptor and HER2 in salivary duct carcinoma (SDC). Adenoid cystic carcinoma is the archetype of slow but relentless disease with perineural spread and late lung metastases; salivary duct carcinoma is aggressive and resembles apocrine breast cancer.

Surgery with post-operative radiotherapy (or neutron/carbon-ion therapy for unresectable ACC) is standard for localised disease; RTOG 1008 tested adding cisplatin. Systemic therapy is subtype-directed: trastuzumab-docetaxel or T-DXd for HER2-positive SDC; androgen deprivation (leuprorelin ± bicalutamide, enzalutamide) for AR-positive SDC; larotrectinib or entrectinib for ETV6-NTRK3 secretory carcinoma; lenvatinib, axitinib or rivoceranib for progressive ACC (~10-15% response, high disease control); and chemotherapy (CAP, carboplatin-paclitaxel) for others. Checkpoint inhibitors have low activity except in a minority with high TMB or PD-L1. Notch-mutant ACC (~15%, aggressive) is a target for gamma-secretase inhibitors.

State of the art today

  • Salivary gland cancer is where fusion-defined pathology has most changed practice: ETV6-NTRK3 secretory carcinoma responds to NTRK inhibitors in ~90%.
  • Salivary duct carcinoma is treated like a HER2+/AR+ breast cancer, with T-DXd giving durable responses.
  • VEGFR inhibitors stabilise adenoid cystic carcinoma but rarely shrink it; NOTCH inhibition targets its worst subset.
  • Carbon-ion therapy for unresectable ACC is an example of particle therapy with a clear niche.
Who it affects

About 1 per 100,000 per year; ~5% of head and neck cancers; more than 20 histologic types, most individually very rare.

Where the cases are

Cases by country · GLOBOCAN 2022
All countries →

No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.

Standard of care

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Localised, resectable

Complete resection (parotidectomy with facial-nerve preservation where possible) and neck dissection for high-grade; post-operative radiotherapy for high-grade, close margins, perineural invasion, T3-4 or node-positive disease.

NCCN · Category 2A
IMRT / IGRT (modern external beam)Proton therapy
Unresectable localised

Definitive radiotherapy; carbon-ion or neutron therapy for adenoid cystic carcinoma where available (COSMIC, Heidelberg).

ESMO salivary gland guideline 2022
Carbon-ion therapyIMRT / IGRT (modern external beam)
Recurrent/metastatic, subtype-directed

HER2+ SDC: trastuzumab + docetaxel or trastuzumab deruxtecan; AR+ SDC: androgen deprivation (leuprorelin/bicalutamide; enzalutamide); NTRK-fused secretory carcinoma: larotrectinib or entrectinib; ACC: lenvatinib or axitinib for progressive disease, observation if indolent.

NCCN · Category 2A
TrastuzumabDocetaxelTrastuzumab deruxtecanEnzalutamideLarotrectinibEntrectinibLenvatinibAxitinib
Recurrent/metastatic, other

Platinum-based chemotherapy (CAP, carboplatin-paclitaxel); pembrolizumab for TMB-H/MSI-H or PD-L1-positive; clinical trials.

NCCN · Category 2A
CisplatinDoxorubicinCyclophosphamideCarboplatinPaclitaxel / nab-paclitaxelPembrolizumab

Subtypes & biomarkers

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Subtypes
  • Adenoid cystic carcinoma (MYB-NFIB; NOTCH1-mutant subset)
  • Mucoepidermoid carcinoma (CRTC1/3-MAML2)
  • Salivary duct carcinoma (AR+, HER2+ in ~30%)
  • Secretory carcinoma (ETV6-NTRK3)
  • Acinic cell carcinoma (NR4A3)
  • Carcinoma ex pleomorphic adenoma
  • Polymorphous adenocarcinoma, myoepithelial and others
Biomarkers clinicians test

Target prevalence in this cancer

History

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  1. 1859Billroth describes 'cylindroma' (adenoid cystic carcinoma)
  2. 1994Neutron therapy trial (RTOG-MRC) in unresectable salivary cancer
  3. 2003CRTC1-MAML2 fusion in mucoepidermoid carcinoma (Tonon)
    Gene fusion
  4. 2009MYB-NFIB fusion in adenoid cystic carcinoma (Persson, PNAS)
  5. 2010Mammary analogue secretory carcinoma with ETV6-NTRK3 described (Skálová)
    NTRK
  6. 2018Larotrectinib approved tumour-agnostically, including secretory carcinoma
    Larotrectinib
  7. 2019Trastuzumab-docetaxel in HER2+ salivary duct carcinoma (Takahashi, JCO); lenvatinib in ACC (Tchekmedyian, JCO)
    TrastuzumabDocetaxelLenvatinib
  8. 2022ESMO-EURACAN salivary gland guideline

Pipeline

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ApprovedADC
Trastuzumab deruxtecan · Enhertu
ApprovedSmall-molecule multi-kinase inhibitor (VEGFR, FGFR, PDGFR, RET, KIT)
Lenvatinib · Lenvima
Not mapped hereSmall-molecule pan-TRK inhibitor (first generation)
Larotrectinib · Vitrakvi
Carbon-ion therapy

Open problems

  • Adenoid cystic carcinoma: no drug induces meaningful shrinkage; 20-year survival remains poor.
  • Trials are tiny; most evidence is phase 2 or retrospective.
  • Facial nerve sacrifice and disfigurement in surgery.
  • Immunotherapy largely inactive.

Trials

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Recruiting now (live from ClinicalTrials.gov)

Recruiting trials near you · live from ClinicalTrials.gov
Salivary gland cancers
condition: Salivary gland cancers
Open on ClinicalTrials.gov →

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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 Salivary gland cancers

Generated from this cancer's standard of care, biomarkers, and pipeline · 15 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 Histotype with fusion confirmation, HER2 IHC/ISH and androgen receptor IHC, NTRK fusion, NOTCH1 mutation, Perineural invasion, grade, margin status), 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 Adenoid cystic carcinoma, Mucoepidermoid carcinoma, Salivary duct carcinoma.
  4. Is germline (inherited) genetic testing recommended for me or my family?
    Why: Inherited variants can change treatment and matter for relatives.

Localised, resectable

  1. For my situation (localised, resectable), which of the standard options do you recommend and why?
    Why: Guideline options include: Complete resection (parotidectomy with facial-nerve preservation where possible) and neck dissection for high-grade; post-operative radiotherapy for high-grade, close margins, perineural invasion, T3-4 or node-positive disease.

Unresectable localised

  1. For my situation (unresectable localised), which of the standard options do you recommend and why?
    Why: Guideline options include: Definitive radiotherapy; carbon-ion or neutron therapy for adenoid cystic carcinoma where available (COSMIC, Heidelberg).

Recurrent/metastatic, subtype-directed

  1. For my situation (recurrent/metastatic, subtype-directed), which of the standard options do you recommend and why?
    Why: Guideline options include: HER2+ SDC: trastuzumab + docetaxel or trastuzumab deruxtecan; AR+ SDC: androgen deprivation (leuprorelin/bicalutamide; enzalutamide); NTRK-fused secretory carcinoma: larotrectinib or entrectinib; ACC: lenvatinib or axitinib for progressive disease, observation if indolent.
  2. Am I a candidate for Trastuzumab, Docetaxel, Trastuzumab deruxtecan or related drugs, and what side effects should I expect?
    Why: Knowing the expected toxicities helps you plan work, family, and supportive care.

Recurrent/metastatic, other

  1. For my situation (recurrent/metastatic, other), which of the standard options do you recommend and why?
    Why: Guideline options include: Platinum-based chemotherapy (CAP, carboplatin-paclitaxel); pembrolizumab for TMB-H/MSI-H or PD-L1-positive; clinical trials.
  2. Am I a candidate for Cisplatin, Doxorubicin, Cyclophosphamide or related drugs, 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 Trastuzumab deruxtecan, Lenvatinib, Larotrectinib, Carbon-ion therapy?
    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 “Adenoid cystic carcinoma: no drug induces meaningful shrinkage; 20-year survival remains poor”. How does that affect my plan?
    Why: Open problems are where trials and second opinions matter most.
  5. I read that “Trials are tiny; most evidence is phase 2 or retrospective”. 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

16
Allogeneic stem cell transplantationAndrogen deprivation & AR pathway inhibitorsAnti-angiogenic therapyAntibody-drug conjugate (ADC)CAR-T cell therapyCarbon-ion therapyCardio-oncologyComprehensive genomic profilingCytotoxic chemotherapyImmune checkpoint inhibitorsIMRT / IGRT (modern external beam)Monoclonal antibodiesPlatinum agentsProton therapySmall-molecule kinase inhibitorsTopoisomerase-I inhibitors (and ADC payloads)

targets

11
ALKAndrogen receptorFGFR2HER2KITMETNTRKPD-1RETROS1VEGF / VEGFR

drugs

14
ApprovedSmall-molecule kinase inhibitor (VEGFR)
Axitinib · Inlyta
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
ApprovedCytotoxic chemotherapy (platinum)
Cisplatin · Platinol (generic)
Not mapped hereAlkylating agent (oxazaphosphorine prodrug)
Cyclophosphamide · Cytoxan / Endoxan
ApprovedCytotoxic chemotherapy (taxane)
Docetaxel · Taxotere (generic)
ApprovedCytotoxic chemotherapy (anthracycline)
Doxorubicin · Adriamycin
Not mapped hereSmall-molecule TRK/ROS1/ALK TKI (CNS-penetrant)
Entrectinib · Rozlytrek
ApprovedSmall-molecule AR antagonist
Enzalutamide · Xtandi
Not mapped hereSmall-molecule pan-TRK inhibitor (first generation)
Larotrectinib · Vitrakvi
ApprovedSmall-molecule multi-kinase inhibitor (VEGFR, FGFR, PDGFR, RET, KIT)
Lenvatinib · Lenvima
ApprovedCytotoxic chemotherapy (taxane)
Paclitaxel / nab-paclitaxel · Taxol / Abraxane
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
ApprovedMonoclonal antibody (anti-HER2)
Trastuzumab · Herceptin (and biosimilars, Phesgo with pertuzumab)
ApprovedADC
Trastuzumab deruxtecan · Enhertu

companies

9
AstellasAstraZenecaBayerDaiichi SankyoEisaiMerck & Co. (MSD)Pfizer (incl. Seagen)Roche / GenentechSanofi

pathways

2
Androgen receptor signallingVEGF angiogenesis

terms

3
Gene fusionRare cancersTumour-agnostic (tissue-agnostic) approval

Latest papers

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Latest papers · live from Europe PMC
Open in Europe PMC

Query for this cancer: (TITLE:"Salivary gland cancers" OR ABSTRACT:"Salivary gland cancers" OR TITLE:"Adenoid cystic carcinoma" OR ABSTRACT:"Adenoid cystic carcinoma" OR TITLE:"Mucoepidermoid carcinoma" OR ABSTRACT:"Mucoepidermoid carcinoma" OR TITLE:"Salivary duct carcinoma" OR ABSTRACT:"Salivary duct carcinoma" OR TITLE:"Secretory carcinoma" OR ABSTRACT:"Secretory carcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Salivary gland cancers, not a curated reading list.

Connected

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Pages like this

not linked directly; found by shared links

technologies

7
Androgen deprivation & AR pathway inhibitorsAntibody-drug conjugate (ADC)Carbon-ion therapyComprehensive genomic profilingIMRT / IGRT (modern external beam)Proton therapySmall-molecule kinase inhibitors

targets

5
Androgen receptorHER2METNTRKVEGF / VEGFR

drugs

14
ApprovedSmall-molecule kinase inhibitor (VEGFR)
Axitinib · Inlyta
ApprovedCytotoxic chemotherapy (platinum)
Carboplatin
ApprovedCytotoxic chemotherapy (platinum)
Cisplatin · Platinol (generic)
Not mapped hereAlkylating agent (oxazaphosphorine prodrug)
Cyclophosphamide · Cytoxan / Endoxan
ApprovedCytotoxic chemotherapy (taxane)
Docetaxel · Taxotere (generic)
ApprovedCytotoxic chemotherapy (anthracycline)
Doxorubicin · Adriamycin
Not mapped hereSmall-molecule TRK/ROS1/ALK TKI (CNS-penetrant)
Entrectinib · Rozlytrek
ApprovedSmall-molecule AR antagonist
Enzalutamide · Xtandi
Not mapped hereSmall-molecule pan-TRK inhibitor (first generation)
Larotrectinib · Vitrakvi
ApprovedSmall-molecule multi-kinase inhibitor (VEGFR, FGFR, PDGFR, RET, KIT)
Lenvatinib · Lenvima
ApprovedCytotoxic chemotherapy (taxane)
Paclitaxel / nab-paclitaxel · Taxol / Abraxane
ApprovedMonoclonal antibody (anti-PD-1)
Pembrolizumab · Keytruda / Keytruda Qlex (SC)
ApprovedMonoclonal antibody (anti-HER2)
Trastuzumab · Herceptin (and biosimilars, Phesgo with pertuzumab)
ApprovedADC
Trastuzumab deruxtecan · Enhertu

companies

4
BayerDaiichi SankyoEisaiRoche / Genentech

pathways

2
Androgen receptor signallingVEGF angiogenesis

terms

3
Gene fusionRare cancersTumour-agnostic (tissue-agnostic) approval