Multiple-Basket Study of Targeted Therapy for Advanced Solid Tumors


Key Points

  • Objective response was observed in 23% of patients overall.
  • High response rates were observed in HER2 amplified/overexpressing colorectal cancer (38%) and BRAF V600 mutated non–small cell lung cancer (43%). 

In a phase IIa multiple-basket study (MyPathway) reported in the Journal of Clinical Oncology, Hainsworth et al found that agents targeting specific molecular alterations produced responses in tumors outside of current labeling for the agents, with high response rates being observed in some tumor types.  

Study Details

In the study, between April 2014 and November 2016, 251 patients with advanced solid refractory tumors of 35 different types received targeted treatment consisting of pertuzumab (Perjeta) plus trastuzumab (Herceptin), erlotinib (Tarceva), vemurafenib (Zelboraf), or vismodegib (Erivedge) for tumors harboring alterations in HER2, EGFR, BRAF, or the Hedgehog pathway, respectively. The primary outcome measure was investigator-assessed objective response rate within each tumor-pathway cohort.

Response Rates

The efficacy population consisted of 230 treated patients evaluated for response or who discontinued treatment before evaluation. Among these, 52 patients (23%) with 14 tumor types had an objective response, including complete response in 4 patients. Responses were observed in:

  • 30 patients (26%) with 9 tumor types among 114 with HER2 amplification/overexpression and in 4 (11%) of 36 with HER2 mutation treated with trastuzumab plus pertuzumab;  
  • 12 patients (46%) with 6 tumor types among 26 with BRAF V600E and in 1 (4%) of 23 with other non-V600 BRAF mutations treated with vemurafenib;
  • 3 patients (14%) of 21 with Hedgehog pathway mutations treated with vismodegib;
  • And 1 (11%) of 9 patients with EGFR mutations treated with erlotinib.

Tumor-pathway cohorts with high objective response rates included HER2 amplified/overexpressing colorectal cancer (14 of 37, 38%) and BRAF V600 mutated non–small cell lung cancer (6 of 14, 43%).

The investigators concluded, “The four currently approved targeted therapy regimens in the MyPathway study produced meaningful responses when administered without chemotherapy in several refractory solid tumor types not currently labeled for these agents.”

The study was supported by Roche/Genentech.

John D. Hainsworth, MD, of Sarah Cannon Research Institute, is the corresponding author for the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.