Real-world effectiveness of molecular-matched therapies in salivary gland cancer

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.