# 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-growing 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, shorter survival); 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]
- Types and stages (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]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/salivary-gland/#finding-it [6 biomarkers]
- Treatment (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]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, 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]
- Biology and targets (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]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/salivary-gland/where-you-are/ [25 centres in the subtypes]
- Decisions and support (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]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, 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, 3 medicines in the subtypes, 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