Several targeted therapies demonstrated clinically meaningful activity among patients with refractory solid tumors expressing particular molecular alterations, according to a study published in the Journal of Clinical Oncology.1

For the phase 2a MyPathway multiple basket study (ClinicalTrials.gov Identifier: NCT02091141), researchers assigned 251 eligible patients to a specific treatment cohort depending on the molecular profile of their tumors.

Patients with HER2 molecular alterations, EGFR-activation mutations, BRAF mutations, and Hedgehog pathway alterations were treated with intravenous pertuzumab plus trastuzumab, oral erlotinib, oral vemurafenib, and oral vismodegib, respectively. Patients who had an objective response (OR) or stable disease (SD) continued treatment and were evaluated every 2 treatment cycles for the first 6 months, then every 3 months thereafter.

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The median follow-up for the efficacy population was 9.7 months. Of the 230 patients included at time of efficacy analysis, 52 (23%) with 14 different tumor types had an OR; 4 and 48 patients had a complete response (CR) and a partial response (PR), respectively.

Among patients with HER2 amplification/overexpression, 30 of 114 (26%) patients had an OR (2 CR, 28 PR) with trastuzumab plus pertuzumab. Patients with colorectal cancer had a notable OR rate, with 14 of 37 patients (38%) reaching a PR. Of the 36 patients with HER2 mutations without amplification/overexpression, 4 had an OR.

Of the 26 patients with a BRAFV600 mutation, an OR was observed in 12 (2 CR, 10 PR) among the 6 different tumor types treated with vemurafenib. Six (43%) patients of the 14 with refractory BRAFV600E-mutated non–small cell lung cancer — comprising the largest cohort in the BRAF arm — had an OR (1 CR, 5 PR).

Three patients of the 21 with Hedgehog pathway mutations had a PR with vismodegib, and 1 of 9 patients with various EGFR mutations had a PR.

The authors concluded that “treatment of additional patients in each of these groups is ongoing to better define the activity of these treatments and to further clarify the importance of molecular and histologic subgroups.”

Reference

  1. Hainsworth JD, Meric-Bernstam F, Swanton C, et al. Targeted therapy for advanced solid tumors o the basis of molecular profiles: results from MyPathway, an open-label, phase IIa multiple basket study. J Clin Oncol. 2018 Jan 10. doi: 10.1200/JCO.2017.75.3780 [Epub ahead of print]

Topics:

General Oncology