“Individual Tumor Profiling: Has Tumor Molecular Profiling Enabled More Effective and Less Toxic Cancer Treatment?” provides an overview of the use of tumor profiling in the nationwide National Cancer Institute (NCI)-Molecular Analysis for Therapy Choice (MATCH) clinical trial for treatment of cancer. This trial is particularly interesting, given the recent US Food and Drug Administration (FDA) approval of KEYTRUDA® (pembrolizumab; Merck), the first approved cancer therapy for solid tumors based on common genetic markers as opposed to initial location of the tumors.
The goal of the NCI-MATCH phase 2 clinical trial, developed by the ECOG-ACRIN Cancer Research Group and the NCI, is to test approved therapeutic agents and investigational agents as treatment for tumors that share particular genetic traits but that may or may not be located in the same tissues. Each arm of the trial consists of the use of these agents, either in isolation or in combination. Among the approximately 30 agents currently being tested, some are commercially available whereas others are in clinical trials and have demonstrated efficacy against certain cancers. These agents are targeted towards about 4,000 different variants in over 140 genes known to be associated with cancer. Patients are matched to the appropriate therapeutic trial arm based on DNA sequencing of tumors. Because patient enrollment is based on specific genetic abnormalities, this trial presents an excellent opportunity for patients with rare cancers that share genetic aberrations with common forms of cancer to participate in a rigorous, large study and explore new, hopefully efficacious, therapeutic options.
The results of a planned interim analysis of data between August and November 2015 demonstrated higher than expected accrual, with sequencing results obtained from 645 (87%) submitted tumor samples. Among these patients, 56 (9%) had a genetic abnormality allowing them to be matched to one of the 10 treatment arms; this matching percentage was close to the expected 10% match rate. Thirty-three of these patients (5%) were eligible to be assigned to a treatment arm, 19 (58%) of whom were diagnosed with uncommon cancers (defined as not breast, colorectal, non-small cell lung, or prostate cancer) and 14 (42%) of whom were diagnosed with common cancers. Among the eligible patients, 16 patients entered 7 treatment arms; the remaining patients did not start treatment due to factors including death, disease progression, and change in eligibility. Overall, the results indicated that the trial was feasible on a national scale and provided guidance on improvements and modifications in factors such as sample handling, patient enrollment, and increased match rate goal (≥ 20%).
As of June 25, 2017, out of 6,000 patients, tumor samples were obtained from 5,957 patients. Of the 5,521 patients who received sequencing results, 986 were matched to an available treatment arm and 675 patients enrolled for treatment. Twenty-six treatment arms are open for patient enrollment, with initial reporting on 19 of the arms. Additional treatment arms are closed/full or in development.
A major criticism of the clinical use of tumor profiling is the lack of strong evidence demonstrating a clear correlation between specific genetic markers and effective treatment strategies. The NCI-MATCH clinical trial may be able to address this issue by providing data on a large-scale to support the use of specific therapeutic agents to treat tumors with specific genetic abnormalities. As new investigational products become available for use in the trial, patients with cancer may also have faster access to different treatment options. Despite the modest match rate, the interim analysis of the trial is promising, and with the recent FDA-approval of pembrolizumab, tumor profiling may become a major therapeutic strategy in clinical settings for patients with cancer.
References:
Conley BA, Gray R, Chen A, O’Dwyer P, Arteaga C, Coffey B, Patton D, Li S, McShane LM, Rubinstein L, Comis R, Abrams J, Williams PM, Lih CJ, Hamilton S, Mitchell E, Zwiebel J, Flaherty K, NCI MATCH team. NCI-molecular analysis for therapy choice (NCI-MATCH) clinical trial: interim analysis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT101
ECOG-ACRIN Cancer Research Group. (2017, June 07). NCI-MATCH cancer trial reaches 6,000-patient tumor sequencing goal 2 years early. Retrieved from https://www.eurekalert.org/pub_releases/2017-06/ecrg-nct060617.php
NCI-MATCH/EAY131. Retrieved from http://ecog-acrin.org/trials/nci-match-eay131 and http://ecog-acrin.org/nci-match-eay131