Meet something new.
Top Line: The NCI-MATCH trial is the first national-scale precision oncology trial in the United States.
The Study: The goal was to leverage a huge pool of potential patients to match tumors having “actionable” mutations with an associated targeted treatment. In one sense, it’s 30 parallel, molecularly driven phase II studies. In another, it’s match.com for tumors and targeted therapy. Nearly 6000 patients with refractory malignancies from over 1000 centers had biopsy specimens sent for centralized molecular profiling. The majority of patients (93%) were successfully profiled, 37.6% had an actionable mutation, and 26.4% were eligible to receive a matched targeted therapy. However, only 17.8% were ultimately assigned to therapy due to the logistics of availability on sub-protocols. Why did only a portion of patients receive matched therapy? Just like your favorite dating app, MATCH didn’t just match tumor and therapy based on a single factor. They had to also account for things like co-existing mutations conferring resistance to the MATCH’d therapy. For example, the most common actionable mutation was in PIK3CA (12%), yet 31% of those patients had mutations that conferred resistance to matched therapy--including the second-most frequent alteration in PTEN. Furthermore, over half of patients had alterations in tumor-suppressor genes that didn’t preclude matched therapy, but are associated with resistance. One standout tumor was cholangiocarcinoma, which had a 25% match rate and a much higher rate of actionable mutations than was seen in the Cancer Genome Atlas.TBL: MATCH demonstrates the feasibility of a large precision oncology trial to pool relatively uncommon molecular alterations and accelerate the discovery of effective therapies. | Flaherty, J Clin Oncol 2020