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Tumor biopsy screening can identify actionable molecular targets

Journal of Clinical Oncology
Reuters Health - 27/11/2020 - Large-scale screening of tumor biopsy specimens from patients with refractory malignancies can identify molecular alterations susceptible to investigational therapies, according to findings from the NCI-MATCH study.

"The most interesting finding of this analysis is the range of 'actionability' observed when deploying next-generation sequencing (NGS) across the wide spectrum of cancer types included in this trial," said Dr. Keith T. Flaherty of Massachusetts General Hospital, in Boston.

"By 'actionability,' we mean the percentage of patients with a given tumor type for which molecular alterations were found that pointed to one of our several dozen treatment arms," he told Reuters Health by email.

NCI-MATCH was the first national-scale trial in the U.S. incorporating centralized diagnostic testing and geographically distributed clinical investigation of dozens of treatment options in parallel.

Dr. Flaherty and colleagues used data from this trial to evaluate the frequency of actionable genetic alterations in nearly 6,000 patients with advanced refractory cancer.

Ninety-three percent of samples were sequenced successfully, and molecular alterations for assignment to an NCI-MATCH subprotocol were present in 37.6% of patients, the researchers report in the Journal of Clinical Oncology.

The actual treatment assignment rate was 17.8% and ranged from 13.7% of patients with colorectal cancer to 17.4% of patients with non-small-cell lung cancer, 17.8% of patients with breast cancer and 23.0% of patients with prostate cancer.

Seventy percent of assigned patients actually received treatment on a subprotocol, and 11 of 30 subprotocols reached an accrual goal of at least 31 eligible patients.

"The rate of accrual was the fastest ever seen in the NCI-supported cooperative group system," Dr. Flaherty said. "This speaks to the attractiveness of this type of platform trial approach; open to the entire spectrum of advanced solid tumors."

Multiple actionable mutations were seen in 11.9% of specimens, and resistance-conferring tumor mutations were seen in 71.3% of specimens.

"Next generation sequencing is an efficient way to identify both approved and promising investigational therapies," Dr. Flaherty said. "For that reason it should be considered standard-of-care for patients with advanced cancers."

"This study sets the benchmark for the actionability of NGS, but we expect that this number 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," he said.

"While we could not identify actionable alterations in the remaining 62%, the rate of actionability has continued to increase since the timeframe in which NCI-MATCH was designed," Dr. Flaherty said.

"The molecular landscape of a population of patients with relapsed, refractory advanced cancer strongly endorses a shift to investigation of combination targeted-therapy regimens in such genetically complex tumors, most notably those harboring multiple actionable alterations," the researchers add.

The study did not have commercial funding.

SOURCE: https://bit.ly/3mm7TP3 Journal of Clinical Oncology, online October 13, 2020.

By Will Boggs MD

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