# Salivary gland cancers

Source: https://onco.cc/cancers/salivary-gland/  
OnCo record `salivary-gland` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-08
- Also known as: Adenoid cystic carcinoma; Mucoepidermoid carcinoma; Salivary duct carcinoma; Secretory carcinoma
- Tags: gap-fill; head-and-neck; rare
- Group: head and neck
- Burden: About 1 per 100,000 per year; ~5% of head and neck cancers; more than 20 histologic types, most individually very rare.
- 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: Histotype with fusion confirmation (MYB, MAML2, ETV6-NTRK3, NR4A3); HER2 IHC/ISH and androgen receptor IHC (salivary duct carcinoma); NTRK fusion (secretory carcinoma); NOTCH1 mutation (adenoid cystic, poor prognosis); Perineural invasion, grade, margin status; PD-L1 / TMB (rarely high)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/salivary-gland/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/salivary-gland/#overview [5 subtypes, 4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/salivary-gland/#what-it-is [12 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/salivary-gland/#finding-it [6 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/salivary-gland/#treating-it [4 settings, 4 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/salivary-gland/#evidence [5 trials, 1 key paper, 8 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/salivary-gland/#science [22 targets, 2 pathways]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/salivary-gland/where-you-are/
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/salivary-gland/#living-with-it [15 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/salivary-gland/coming/ [16 medicines, 5 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/salivary-gland/data/ [83 connected records]

## Standard of care

- 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. ([IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Proton therapy](https://onco.cc/technologies/proton-therapy/))
- Unresectable localised: Definitive radiotherapy; carbon-ion or neutron therapy for adenoid cystic carcinoma where available (COSMIC, Heidelberg). ([Carbon-ion therapy](https://onco.cc/technologies/carbon-ion/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/))
- 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. ([Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Docetaxel](https://onco.cc/drugs/docetaxel/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/), [Enzalutamide](https://onco.cc/drugs/enzalutamide/), [Larotrectinib](https://onco.cc/drugs/larotrectinib/), [Entrectinib](https://onco.cc/drugs/entrectinib/), [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Axitinib](https://onco.cc/drugs/axitinib/))
- Recurrent/metastatic, other: Platinum-based chemotherapy (CAP, carboplatin-paclitaxel); pembrolizumab for TMB-H/MSI-H or PD-L1-positive; clinical trials. ([Cisplatin](https://onco.cc/drugs/cisplatin/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/))

## State of the art

- 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.

## 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Salivary_gland_tumour
- NCCN Guidelines: Head and Neck Cancers: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437
- ESMO-EURACAN salivary gland guideline (2022): https://doi.org/10.1016/j.esmoop.2022.100602
- Adenoid Cystic Carcinoma Research Foundation: https://www.accrf.org/

## Connected records

- technologies: [Androgen deprivation & AR pathway inhibitors](https://onco.cc/technologies/androgen-deprivation/), [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Carbon-ion therapy](https://onco.cc/technologies/carbon-ion/), [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Proton therapy](https://onco.cc/technologies/proton-therapy/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [Androgen receptor](https://onco.cc/targets/androgen-receptor/), [CRTC1](https://onco.cc/targets/crtc1/), [ESRRA](https://onco.cc/targets/esrra/), [HER2](https://onco.cc/targets/her2/), [MET](https://onco.cc/targets/met/), [NOTCH1](https://onco.cc/targets/notch1/), [NOTCH2](https://onco.cc/targets/notch2/), [NTRK](https://onco.cc/targets/ntrk/), [PPP2R1A](https://onco.cc/targets/ppp2r1a/), [RUNX1](https://onco.cc/targets/runx1/), [SMARCA2](https://onco.cc/targets/smarca2/), [SPEN](https://onco.cc/targets/spen/), [TRRAP](https://onco.cc/targets/trrap/), [TYW2](https://onco.cc/targets/tyw2/), [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- drugs: [Axitinib](https://onco.cc/drugs/axitinib/), [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Docetaxel](https://onco.cc/drugs/docetaxel/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Entrectinib](https://onco.cc/drugs/entrectinib/), [Enzalutamide](https://onco.cc/drugs/enzalutamide/), [Gotistobart](https://onco.cc/drugs/gotistobart/), [Larotrectinib](https://onco.cc/drugs/larotrectinib/), [Lenvatinib](https://onco.cc/drugs/lenvatinib/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [REM-422](https://onco.cc/drugs/rem-422/), [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- companies: [Bayer](https://onco.cc/companies/bayer/), [Daiichi Sankyo](https://onco.cc/companies/daiichi-sankyo/), [Eisai](https://onco.cc/companies/eisai/), [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- pathways: [Androgen receptor signalling](https://onco.cc/pathways/ar-signaling/), [VEGF angiogenesis](https://onco.cc/pathways/vegf-angiogenesis/)
- terms: [Gene fusion](https://onco.cc/terms/gene-fusion/), [Rare cancers](https://onco.cc/terms/rare-cancers/), [Tumour-agnostic (tissue-agnostic) approval](https://onco.cc/terms/tumour-agnostic/)
- key papers: [Salivary gland cancer: ESMO-European Reference Network on Rare Adult Solid Cancers (EURACAN) Clinical Practice Guideline for diagnosis, treatment and follow-up](https://onco.cc/key-papers/paper-van-herpen-esmo-open/)
- biomarkers: [NTRK1/2/3 gene fusion](https://onco.cc/biomarkers/ntrk-fusion/)
- journals: [Head and neck pathology](https://onco.cc/journals/head-and-neck-pathology/)
- cancers: [Acinic cell carcinoma of the salivary glands](https://onco.cc/cancers/acinic-cell-carcinoma-salivary/), [Adenoid cystic carcinoma](https://onco.cc/cancers/adenoid-cystic-carcinoma/), [Carcinoma ex pleomorphic adenoma](https://onco.cc/cancers/carcinoma-ex-pleomorphic-adenoma/), [Mucoepidermoid carcinoma](https://onco.cc/cancers/mucoepidermoid-carcinoma/), [Salivary duct carcinoma](https://onco.cc/cancers/salivary-duct-carcinoma/)
- trials: [A Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma](https://onco.cc/trials/nct04325828/), [A Study of Emiltatug Ledadotin (Emi-Le) in Participants With Solid Tumors](https://onco.cc/trials/nct05377996/), [Clinical Trial of HG146 Administered to Participants with Adenoid Cystic Carcinoma](https://onco.cc/trials/nct06781567/), [Study of REM-422 in Patients With Recurrent, Metastatic, or Unresectable Adenoid Cystic Carcinoma](https://onco.cc/trials/nct06118086/), [VMD-928 Monotherapy and in Combination With Pembrolizumab to Treat TrkA Overexpression Driven Solid Tumors or Lymphoma](https://onco.cc/trials/nct03556228/)

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JSON: https://onco.cc/api/v1/entities/salivary-gland.json