Results from MyPathway, a phase IIa multiple basket study, provide a proof-of-principle for matching patients to effective, chemotherapy-free treatment of tumours based on molecular characteristics rather than site of origin. It is a particularly valuable opportunity for cancer patients with limited treatment options or who are unable to tolerate traditional chemotherapies. Data published in March issue of the Annals of Oncology suggest that matched targeted therapy for salivary gland carcinoma has promising efficacy and support molecular profiling in treatment determination.
The incidence of salivary gland cancer has risen from 10.4 per 1 000 000 in 1973 to 16 per 1 000 000 in 2009. Advanced salivary gland carcinomas are particularly unresponsive to traditional chemotherapies.
MyPathway is a phase IIa study that evaluates targeted therapies in non-indicated tumour types with actionable molecular alterations. In the Annals of Oncology, the study team led by Dr. Razelle Kurzrock of the Moores Cancer Center, UC San Diego, San Diego, USA presented the efficacy and safety results for a subgroup of MyPathway patients with advanced salivary gland cancer matched to targeted therapies based on tumour molecular characteristics.
The study team explained that MyPathway is an ongoing, multiple basket, open-label, non-randomised, multicentre study. This trial design allows to address treatment efficacy in both common and rare tumour types, regardless of their site of origin.
Patients with advanced salivary gland carcinoma included in the study received pertuzumab plus trastuzumab for HER2 alteration, vismodegib for PTCH-1/SMO mutation, vemurafenib for BRAF V600 mutation, or atezolizumab in case of high tumour mutational burden (TMB).
The study primary endpoint is the objective response rate (ORR).
As of 15 January 2018, 19 patients with salivary gland carcinoma were enrolled and treated; of those 15 with HER2 amplification and/or overexpression and one each with a HER2 mutation without amplification or overexpression, PTCH-1 mutation, BRAF mutation, and high TMB.
In the 15 patients with HER2 amplification/overexpression (with or without mutations) who were treated with pertuzumab plus trastuzumab, 9 had an objective response (of those, 1 complete response and 8 partial responses) resulting with an ORR of 60% and median response duration of 9.2 months.
The clinical benefit rate, defined by patients with ORs 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 one patient with a HER2 mutation treated with pertuzumab plus trastuzumab (PFS 11.0 months). Partial responses were observed in one patient with the PTCH-1 mutation treated with vismodegib (PFS 14.3 months), one patient with BRAF mutation treated with vemurafenib (PFS 18.5 months), and one patient with high TMB treated with atezolizumab (PFS 5.5+ months).
Safety for each treatment was consistent with previously reported safety profiles.
The study team concluded that overall, 12 of 19 patients (63%) with advanced salivary gland carcinoma, treated with chemotherapy-free regimens matched to specific molecular alterations, experienced an OR. Therefore, data from MyPathway suggest that matched targeted therapy for salivary gland carcinoma has promising efficacy, supporting molecular profiling in treatment determination.
This work was supported by F. Hoffmann-La Roche/Genentech.
Kurzrock R, Bowles DW, Kang H, et al. Targeted therapy for advanced salivary gland carcinoma based on molecular profiling: results from MyPathway, a phase IIa multiple basket study. Annals of Oncology 2020; 31(3):412-421. doi: 10.1016/j.annonc.2019.11.018.