August 24 2021
Philadelphia, PA – A combination of metformin and chemoradiation in patients with locally advanced non-small cell lung cancer (LA-NSCLC) was not found to add survival benefit in the NRG Oncology clinical trial NRG-LU001. These results were recently published in JAMA Oncology.
NRG-LU001 enrolled 170 patients between August 2014 and December 2016, of which 167 were included. 81 patients were randomized to the control arm and 86 patients were randomized to the experimental arm. The control group patients received 60 Gy of radiation combined with concurrent weekly carboplatin and paclitaxel chemotherapy, followed by 2 cycles of consolidative chemotherapy every 3 weeks. The experimental group received the same regimen as the control group, combined with metformin during both the concurrent and consolidation phases of cytotoxic therapy.
The primary outcome was a 1-year progression-free survival (PFS), which was designed to detect 15% improvement in PFS from 50% to 65%. After one year, PFS was 60.4% in the control group and 51.3% in the metformin group. In the Intention-to-Treat analysis, one-year overall survival (OS) was nearly statistically identical, with the control arm at 80.2% OS and the metformin group at 80.8%. Although there were numerically fewer deaths at one year in the metformin arm (24 of 34) than the control group (30 of 33), the discrepancy was due to an increased number of deaths from causes unrelated to lung cancer. There were no statistically significant differences in adverse events (AEs) observed between the control group and metformin group.
“Although metformin did not improve outcomes in this study, we are heartened by the excellent clinical outcomes in both arms compared to previous studies. Moreover, metformin may still have a role to play in NSCLC management, as it appears to affect tumor metabolism in NSCLC patients and may improve outcomes in combination with targeted therapy,” said Heath Skinner, MD, PhD, of the UPMC Hillman Cancer Center, and the co-lead investigator of the NRG-LU001 manuscript.
This project was supported by grants U10CA180822 (NRG Oncology SDMC), U10CA180868 (NRG Oncology Operations), UG1CA189867 (NCORP), U24CA180803 (IROC), U10CA37422 (CCOP), U10CA21661 (RTOG-Ops-Stat) from the National Cancer Institute (NCI).
Citation
Skinner H, Hu C, Tsakiridis T, et al. Addition of Metformin to Concurrent Chemoradiation in Patients With Locally Advanced Non–Small Cell Lung Cancer: The NRG-LU001 Phase 2 Randomized Clinical Trial. JAMA Oncol. Published online July 29, 2021. doi:10.1001/jamaoncol.2021.2318
About NRG Oncology
NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network.