From the Journals

‘Tour de force’ study reveals therapeutic targets in 38% of cancer patients



A national effort to perform genotype drug matching across cancer types shows the value of next-generation sequencing and provides a roadmap for future precision oncology trials, according to experts.

Keith Flaherty, MD, is the lead investigator for the NCI-MATCH trial Massachusetts General Hospital

Dr. Keith Flaherty

The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.

The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.

Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.

“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.

“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”

Relapsed/refractory vs. primary tumors

The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.

The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.

Graphic depicting how NCI-MATCH trial works ECOG-ACRIN Cancer Research Group

NCI-MATCH is a precision medicine cancer trial that seeks to determine whether matching certain drugs or drug combinations in adults whose tumors have specific gene abnormalities will effectively treat their cancer, regardless of their cancer type.

“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”


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