Metformin does not improve efficacy of chemo in non-small cell lung cancer: JAMA
Ontario, Canada: Metformin addition to chemoradiotherapy may be associated with worse treatment efficacy and increased toxicity in patients with non-small cell lung cancer (NSCLC) compared with combined modality therapy alone, show findings from the OCOG-ALMERA trial.
Based on the findings published in the journal JAMA Oncology, the researchers recommended against metformin use as an adjunct to chemoradiotherapy in patients with locally advanced-NSCLC (LA-NSCLC) who do not have diabetes.
LA-NSCLC shows poor survival outcomes even after aggressive concurrent chemoradiotherapy. However, it needs to be studied whether metformin, a diabetes agent that inhibits the mitochondria oxidative phosphorylation chain, could improve chemotherapy and radiotherapy response in LA-NSCLC. To study the same, Theodoros Tsakiridis, Juravinski Cancer Center, Hamilton Health Science, Hamilton, Ontario, Canada, and colleagues examined whether metformin could improve outcomes in patients with LA-NSCLC when given concurrently with chemoradiotherapy and as consolidation treatment.
The Ontario Clinical Oncology Group Advanced Lung Cancer Treatment With Metform in and Chemoradiotherapy (OCOG-ALMERA) study was a multicenter phase 2 randomized clinical trial. Patients were stratified for stage IIIA vs IIIB LA-NSCLC and use of consolidation chemotherapy. The trial enrolled 96 patients with unresected LA-NSCLC who did not have diabetes.
54 patients were randomized to receive platinum-based chemotherapy, concurrent with chest radiotherapy (60-63 Gy), with or without consolidation chemotherapy or the same treatment plus metformin, 2000 mg/d, during chemoradiotherapy and afterward for up to 12 months.
The primary outcome was the proportion of patients who experienced a failure event (ie, locoregional disease progression, distant metastases, death, and discontinuation of trial treatment or planned evaluations for any reason within 12 months).
The trial was stopped early due to slow accrual. Given below are the study's key findings:
- Treatment failure was detected in 18 patients (69.2%) receiving metformin within 1-year vs 12 (42.9%) control patients.
- The 1-year progression-free survival rate was 34.8% in the metformin arm and 63.0% in the control arm (hazard ratio, 2.42).
- The overall survival rates were 47.4% in the metformin arm and 85.2% in the control arm (hazard ratio, 3.80).
- More patients in the experimental arm vs control arm (53.8% vs 25.0%) reported at least 1 grade 3 or higher adverse event.
"In this randomized clinical trial, the addition of metformin to chemoradiotherapy was associated with worse treatment efficacy and increased toxic effects compared with combined modality therapy alone," wrote the authors. "Metformin is not recommended in patients with LA-NSCLC who are candidates for chemoradiotherapy."
Reference:
Tsakiridis T, Pond GR, Wright J, et al. Metformin in Combination With Chemoradiotherapy in Locally Advanced Non–Small Cell Lung Cancer: The OCOG-ALMERA Randomized Clinical Trial. JAMA Oncol. 2021;7(9):1333–1341. doi:10.1001/jamaoncol.2021.2328
