Targeted therapy for advanced salivary gland carcinoma based on molecular profiling: results from MyPathway, a phase IIa multiple basket study

Abstract Background Systemic therapy options for salivary cancers are limited. MyPathway (NCT02091141), a phase IIa study, evaluates targeted therapies in non-indicated tumor types with actionable molecular alterations. Here, we present efficacy and safety results for a subgroup of MyPathway patients with advanced salivary gland cancer (SGC) matched to targeted therapies based on tumor molecular characteristics. Patients and Methods MyPathway is an ongoing, multiple basket, open-label, non-randomized, multi-center study. Patients with advanced SGC received pertuzumab + trastuzumab (HER2 alteration), vismodegib (PTCH-1/SMO mutation), vemurafenib (BRAF V600 mutation), or atezolizumab (high tumor mutational burden [TMB]). The primary endpoint is objective response rate (ORR). Results As of January 15, 2018, 19 patients with SGC were enrolled and treated in MyPathway (15 with HER2 amplification and/or overexpression and one each with HER2 mutation without amplification or overexpression, PTCH-1 mutation, BRAF mutation, and high TMB). In the 15 patients with HER2 amplification/overexpression (+/- mutations) who were treated with pertuzumab + trastuzumab, nine had an objective response (one complete response, eight partial responses) for an ORR of 60% (9.2 months median response duration). Clinical benefit rate (defined by patients with objective responses or stable disease >4 months) was 67% (10/15), median progression-free survival (PFS) was 8.6 months, and median overall survival was 20.4 months. Stable disease was observed in the patient with a HER2 mutation (pertuzumab + trastuzumab, n=1/1, PFS 11.0 months), and partial responses in patients with the PTCH-1 mutation (vismodegib, n=1/1, PFS 14.3 months), BRAF mutation (vemurafenib, n=1/1, PFS 18.5 months), and high TMB (atezolizumab, n=1/1, PFS 5.5+ months). No unexpected toxicity occurred. Conclusions Overall, 12 of 19 patients (63%) with advanced SGC, treated with chemotherapy-free regimens matched to specific molecular alterations, experienced an objective response. Data from MyPathway suggest that matched targeted therapy for SGC has promising efficacy, supporting molecular profiling in treatment determination.