NCI-MATCH Supports Using NGS to Triage Patients to Investigational Therapy

Findings from the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) support the feasibility and efficiency of using next-generation sequencing (NGS) to triage patients to investigational therapy, provided that a sufficiently large pool of agents is made available.¹

Importantly, this is the largest data set ever compiled on patients with tumors that have progressed on 1 or more standard treatments, or with rare cancers for which there is no standard treatment.

“Our exhaustive efforts to enlist all of the promising agents in NCI-MATCH established a new benchmark for the utility of next-generation sequencing in the conduct of clinical trials,” lead author Keith T. Flaherty, MD, a medical oncologist at Massachusetts General Hospital Cancer Center in Boston, said in a press release.² “With time, the efficiency of using tumor genetic testing for broad-based clinical investigation will only increase.”

In this study published in the Journal of Clinical Oncology, tumor biopsy specimens from 5954 patients with refractory malignancies at 1117 accrual sites were centrally analyzed using NGS and selected immunohistochemistry in a master screening protocol. Notably, researchers only evaluated treatments which had demonstrated clear evidence of clinical benefit or at least promising preliminary efficacy in the proposed eligibility genotype in any tumor histology.

Overall, molecular profiling was found to be successful in 93.0% of specimens. Moreover, an actionable alteration was detected in 37.6%.

Following the application of clinical and molecular exclusion criteria, 17.8% of specimens were assigned, though 26.4% could have been assigned if all subprotocols had been available simultaneously. As of the study publication, 11 subprotocols had reached their accrual goal.

Notably though, actionability rates differed among histologies; for instance, the actionability rate for urothelial cancers was 35%, while for pancreatic and small-cell lung cancer the actionability rate was 6%. Additionally, multiple actionable or resistance-conferring tumor mutations were seen in 11.9% and 71.3% of specimens, respectively.

According to researchers, these rates may increase as more drugs become available, especially those that target common gene defects.

“The 6000-patient analysis from NCI-MATCH describes the genetic complexity that is characteristic of relapsed, refractory cancers,” Peter J. O’Dwyer, MD, a medical oncologist at the University of Pennsylvania and group co-chair of the ECOG-ACRIN Cancer Research Group, said in the release. “This publication represents an important milestone in the oncology field’s efforts to translate a genetic understanding of cancer into improved treatments.”

NCI-MATCH researchers also compared the tumor gene make-up of patients with 7 cancer types against The Cancer Genome Atlas (TCGA), including breast, bile duct, cervical, colorectal, lung, pancreatic, and prostate cancer. Ultimately, there were not many differences observed between the primary and metastatic databases. Known resistance mutations to targeted therapies were found to be numerically more frequent in NCI-MATCH than TCGA tumors, though not markedly so.

In order to better understand the differences in tumor gene make-up between primary and metastatic tumors, the investigators plan to compare the NCI-MATCH patients’ primary and metastatic tumors moving forward. Multiple treatment arms have also been opened in NCI-MATCH, with 38 arms of research currently ongoing.

“NCI-MATCH is a unique and ground-breaking trial that will continue to make major contributions in years to come as genomic findings from individual treatment arms, correlated with outcomes, are released,” Lyndsay Harris, MD, translational co-chair of NCI-MATCH and associate director of the Cancer Diagnosis Program and the Division of Cancer Treatment and Diagnosis at the NCI, said in the release.

References:

1. Flaherty KT, Gray RJ, Chen AP, et al. Molecular Landscape and Actionable Alterations in a Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH). Journal of the National Cancer Institute. doi: 10.1200/JCO.19.03010

2. Genomic study of 6000 NCI-MATCH cancer patients leads to new clinical trial benchmarks [news release]. Philadelphia. Published October 13, 2020. Accessed October 14, 2020. https://ecog-acrin.org/news-and-info/press-releases/genomic-study-of-6000-nci-match-cancer-patients-leads-to-new-clinical-trial-benchmarks