Locally Advanced NSCLC: Outcomes With Metformin Plus Chemoradiotherapy
Posted: Tuesday, November 30, 2021
A study conducted by Mark Levine, MD, of Juravinski Cancer Center, Hamilton Health Science, Ontario, Canada, and colleagues determined that the addition of the diabetes medication metformin to chemoradiotherapy is not recommended for patients with locally advanced non–small cell lung cancer (NSCLC) due to poor treatment efficacy and increased toxicity. The results of this study, which were published in JAMA Oncology, also reported an increase in a failure event within 12 months with the addition of metformin.
This phase II study from the Ontario Clinical Oncology Group enrolled 54 patients with unresected, locally advanced NSCLC who did not have diabetes. Participants were administered platinum-based chemotherapy concurrently with radiotherapy, with or without consolidation chemotherapy. Metformin (n = 25) was started 2 weeks before standard therapy at 1,000 mg/day, increasing to 1,500 mg/day at week 2 and then to 2,000 mg/day at the start of chemotherapy for up to 12 months.
Among patients given metformin, 56% completed two cycles of chemotherapy, and five individuals did not complete treatment. Only one cycle of chemotherapy was received by seven patients due to adverse events or patient withdrawal. In the control arm, however, 77.8% of patients completed two chemotherapy cycles. Treatment failure was detected in 18 patients treated with metformin as well as 12 patients who did not receive the drug.
Notably, the 1-year estimated progression-free survival was significantly lower for patients given metformin versus those who were not (34.8% vs. 63.0%, hazard ratio [HR] = 2.42). The overall survival for patients treated with metformin was 47.4%, which was still significantly worse than that for participants in the control group (85.2%, HR = 3.80). More than half of patients (n = 14) in the metformin arm experienced at least one grade 3 or higher adverse event, whereas one-quarter of patients (n = 7) in the control arm did, with lung infections and esophagitis being the most common events in patients administered metformin.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
