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Updated: May 3, 2026
Retroductal Submandibular Gland Instillation and Localized Fractionated Irradiation in a Rat Model of Salivary Hypofunction
Published on: April 24, 2016
Real-world effectiveness of molecular-matched therapies in salivary gland cancer
J A M Weijers1, N J van Ruitenbeek1, A C H van Engen-van Grunsven2
1Department of Medical Oncology, Radboud Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, Netherlands.
Background:
Salivary gland cancer (SGC) is a rare cancer comprising over 20 subtypes. Although its molecular landscape is increasingly characterised, real-world data on molecular-matched therapies (MMTs) remain limited, and predictive biomarkers are needed.
Patients And Methods:
Since 2017, real-world data of patients with SGC attending the outpatient clinic at Radboud university medical center have been systematically collected. Best overall response to MMT was assessed per RECIST v1.1. Median progression-free survival (mPFS) was estimated using Kaplan-Meier statistics and compared between the molecular subgroups using the log-rank test.
Results:
At data cutoff, the database contained 662 patients with SGC, including 464 patients with recurrent and/or metastatic disease. Among them, 381 patients exhibited ≥1 molecular alteration, of whom 54% received MMT. Among patients with salivary duct carcinoma (SDC), 83% of patients with ≥1 molecular alteration received MMT, compared with 25% with adenoid cystic carcinoma. In 110 patients with SDC, mPFS with any first-line androgen receptor axis-targeted therapy was 5.3 months [95% confidence interval (CI) 3.5-7.2 months] and was significantly longer in HRAS-mutant (19.1 months; 95% CI 11.0-27.2 months; n = 18) versus HRAS-wild-type cases (3.8 months; 95% CI 2.0-5.6 months; n = 64; P = 0.007). With the first human epidermal growth factor receptor 2-targeted therapy given (n = 35), mPFS was 8.5 months (95% CI 6.4-10.6 months), with objective responses in 61% of RECIST-assessable patients (n = 28). Additionally, objective responses were achieved with other MMTs, including vemurafenib/cobimetinib in BRAF V600E-mutant SDC (n = 3), larotrectinib in secretory carcinoma with ETV6::NTRK3 gene fusions (n = 2), and ipilimumab/nivolumab in mucoepidermoid carcinoma with high tumour mutational burden (n = 1).
Conclusions:
Comprehensive molecular testing in SGC may allow access to MMT, with a subset of patients experiencing clinical benefit from this strategy.
Insights
Molecular-matched therapies (MMTs) show clinical benefit in a subset of salivary gland cancer (SGC) patients. Comprehensive molecular testing can improve access to these targeted treatments for rare cancers.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Salivary gland cancer (SGC) is a rare malignancy with over 20 subtypes.
- Limited real-world data exists on molecular-matched therapies (MMTs) for SGC.
- Predictive biomarkers are needed to guide treatment decisions.
Purpose of the Study:
- To evaluate the real-world effectiveness of molecular-matched therapies (MMTs) in patients with salivary gland cancer (SGC).
- To assess the association between molecular alterations and treatment response in SGC.
- To identify potential predictive biomarkers for MMTs in SGC.
Main Methods:
- Systematic collection of real-world data for SGC patients since 2017.
- Assessment of treatment response using RECIST v1.1 criteria.
- Kaplan-Meier analysis for progression-free survival (PFS) and log-rank tests for subgroup comparisons.
Main Results:
- Out of 662 SGC patients, 381 had molecular alterations, with 54% receiving MMTs.
- Salivary duct carcinoma (SDC) patients with molecular alterations had higher MMT rates (83%) than adenoid cystic carcinoma (25%).
- HRAS-mutant SDC patients showed significantly longer mPFS (19.1 months) with androgen receptor axis-targeted therapy compared to HRAS-wild-type (3.8 months).
- HER2-targeted therapy yielded mPFS of 8.5 months with 61% objective response rate.
- Objective responses observed with BRAF, NTRK, and immunotherapy-based MMTs in specific SGC subtypes.
Conclusions:
- Comprehensive molecular testing in SGC facilitates access to MMTs.
- A subset of SGC patients experiences clinical benefit from MMTs.
- MMTs represent a promising treatment strategy for molecularly selected SGC patients.
