Phase 2 Basket Trial Results Claim Success in BRaf V600-Mutated Cancers

A new clinical trial design that sorts patients based on the mutations in their tumor rather than the tumor type has generated encouraging results. Conducted by researchers at the Memorial Sloan Kettering Cancer Center, phase 2 results from a basket trial evaluated the effect of vemurafenib on nonmelanoma BRaf V600-mutated cancers in 122 patients across 23 global centers.

While the drug vemurafenib was developed to treat BRaf V600-mutated melanoma, in the current study, published in the New England Journal of Medicine, individuals with lung, ovarian, and colorectal cancer (CRC) as well as with some other rare diseases were included. The primary endpoint was response rate (RR) and the secondary endpoints were progression-free survival (PFS) and overall survival.

In the cohort with non-small cell lung cancer, the RR was 42% with a PFS of 7.3 months. In the cohort with Erdheim—Chester disease or Langerhans’-cell histiocytosis, the RR was 43%; the median treatment duration was 5.9 months and no patients had disease progression during therapy. CRC patients who received monotherapy with vemurafenib did not show any response; the median PFS in the group was 4.5 months and median OS was 9.3 months. Of the CRC patients who were treated with the combination of vemurafenib and cetuximab, 50% had tumor regression; median PFS was 3.7 months and median OS was 7.1 months. Among the other tumor types, responses were observed in patients with anaplastic thyroid cancer, cholangiocarcinoma, salivary-duct cancer, soft-tissue sarcoma, and ovarian cancer. Sustained year-long responses were observed in some of these patients. Multiple myeloma patients, the paper reports, did not respond to the drug.

“This study is the first deliverable of precision medicine. We have proven that histology-independent, biomarker-selected basket studies are feasible and can serve as a tool for developing molecularly targeted cancer therapy,” said José Baselga, MD, PhD, the study’s senior author, in a press release. “While we can—and should—be cautiously optimistic, this is what the future of precision medicine looks like.”