Reference Detail

Ref Type

Journal Article

PMID

(32067683)

Authors

Kurzrock R, Bowles DW, Kang H, Meric-Bernstam F, Hainsworth J, Spigel DR, Bose R, Burris H, Sweeney CJ, Beattie MS, Blotner S, Schulze K, Cuchelkar V, Swanton C

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of oncology : official journal of the European Society for Medical Oncology	31	3	2020 Mar	412-421	Ann Oncol

URL

Abstract Text

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 the 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.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 the objective response rate (ORR).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 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 + trastuzumab, 9 had an objective response (1 complete response, 8 partial responses) for an ORR of 60% (9.2 months median response duration). The 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.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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF V600E	salivary gland carcinoma	predicted - sensitive	Vemurafenib	Case Reports/Case Series	Actionable	In a Phase II (MyPathway) trial, Zelboraf (vemurafenib) treatment resulted in a partial response in a patient with advanced salivary gland carcinoma harboring BRAF V600E, with a progression-free survival of 18.5 months (PMID: 32067683; NCT02091141).	32067683