Regulatory Agency Perspective
Aug 01, 2017
NCI Helping to Save Lives and Improve Cancer Survival Rates
Scientific data from clinical trials are essential for evaluating new cancer treatments and setting new standards of care for patients. The National Cancer Institute (NCI) has supported clinical trials for over 50 years through the Cooperative Group Program, which has produced many important improvements in cancer care. Following recommendations in a report issued by the Institute of Medicine in 2010, the Cooperative Group Program has been reorganized into the National Clinical Trials Network (NCTN), with an increased emphasis placed on collaboration.
NCI-funded Network trials have influenced state-of-the-art care in many treatment areas, including the introduction of new drugs, but also by conducting trials that are beyond the scope of the pharmaceutical industry. In 2011, the results of a phase 3 trial at the Radiation Therapy Oncology Group RTOG 9410 showed concurrent chemoradiation therapy conferred long-term survival benefits over sequential treatments in patients with stage III non-small cell lung cancer, an important improvement in outcomes that was achieved with currently existing treatments.1
In a study presented at the ASCO annual meeting this year, Joseph M. Unger, PhD, from the SWOG Statistical Center at the Fred Hutchinson Cancer Research Center in Seattle, WA, and colleagues tried to quantify the impact of NCI-funded cancer trials on patient survival.2 Dr. Unger and his coauthors estimated that through 2015, 3.34 million life-years were gained among US patients at a cost of $125 per life year, a survival improvement that could provide 5.6 more life-years to each of the approximately 600,000 individuals who died of cancer in the US in 2016. Jeff Abrams, MD, Acting Director for Clinical Research and Associate Director of the Cancer Therapy Evaluation Program in the Division of Cancer Treatment & Diagnosis at the NCI, spoke with IASLC Lung Cancer News about this study as well as the broader benefits of the NCTN. Dr. Abrams noted that “there have been many positive Group trials showing an improvement in survival”; such successes include tamoxifen and aromatase inhibitors for adjuvant breast cancer treatment, trastuzumab for adjuvant breast cancer treatment, taxol for adjuvant breast cancer therapy, chemotherapy for adjuvant colon cancer therapy, and chemotherapy for low grade brain tumors, among others. However, the systematic approach of Unger et al. to look across all studies and diseases was a unique one.
“This publicly supported trials Network aims to complement the treatment strategies that are supported by industry,” said Dr. Abrams. “Thus, this Network studies rare cancers and pediatric cancer, and does radiation and surgical trials, areas in which industry does not conduct many trials. It also does many drug trials in partnership with industry but tries to avoid duplicating trials industry would do by themselves. As the Unger paper demonstrates, over the many years of its existence, these Network trials have provided evidence that has served to save and prolong the lives of many Americans with cancer. It has done this at a cost for each year of life gained that seems well worth the investment.”
Promoting collaborative efforts between industry and other partners is a crucial role of the NCI’s Network trials, and these partnerships are increasingly important in the age of precision medicine. Enrolling enough patients with specific molecular profiles to test many targeted therapies is difficult for pharmaceutical companies, according to Dr. Abrams. “By working with NCI and the NCTN, these companies can cast a broad net to attract patients, leverage the NCI standing infrastructure, and cost-share regarding the diagnostic testing required to screen the tumors,” he said. “This provides ample incentives for the industry partners and provides patients with options they might not otherwise have.”
Examples of such collaborations between government, academic, commercial, and nonprofits include the NCI Molecular Analysis for Therapy Choice (NCI-MATCH; EAY131) trial and the Lung-MAP (SWOG S1400) trial. Both of these trials are testing targeted therapies for cancer depending on genetic testing of the patients and the tumors.
Enrolling patients with solid tumors, lymphomas, or myeloma that has progressed on standard treatment or for which there is no standard treatment, NCI-MATCH is a phase 2 precision medicine trial intended to identify targeted drugs or combinations of drugs that produce responses in these patients. Launched in August 2015, NCI-MATCH was spearheaded, in part, by Robert Comis, MD, Co-Chair of ECOG-ACRIN Cancer Research Group, whose death on May 10, 2017, was mourned by the cancer community. Dr. Comis worked with NCI to design and implement the MATCH trial, billed as “the largest, most scientifically rigorous precision medicine cancer trial to date.” Patients are assigned to treatment arms based on the mutational profile of their tumors, genomic sequencing, and other tests. There are over 24 different treatment arms, and more are set to open later this year. The primary endpoint of NCI-MATCH is objective response rate, and treatments will be considered promising if ≥16% of patients have an objective response.
The Lung-MAP trial (S1400) is another precision medicine trial involving collaborations between many partners, including the NCI, NCTN, SWOG, Friends of Cancer Research, the Foundation for the National Institutes of Health, a large number of pharmaceutical companies, Foundation Medicine, and several lung cancer advocacy organizations. In Lung-MAP, enrolled patients with advanced squamous cell lung cancer enter a master protocol in which the genotype of the tumor is used to sort patients into different treatment arms. This study will soon expand to include adenocarcinomas of the lung as well. ✦
1. Curran WJ Jr, Paulus R, Langer CJ, et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011;103:1452-1460.
2. Unger JM, LeBlanc M, Blanke CD. The effect of positive SWOG treatment trials on survival of patients with cancer in the us population. JAMA Oncol. 2017 Jun 5. DOI: 10.1001/jamaoncol. 2017.0762. [Epub ahead of print].