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Addition of Metformin to Chemoradiotherapy for Locally Advanced NSCLC


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As reported in JAMA Oncology by Tsakiridis et al, the Canadian phase II OCOG-ALMERA trial, which was closed early due to slow accrual, showed that the addition of metformin to chemoradiation therapy was associated with worse outcomes in patients with unresected locally advanced non­–small cell lung cancer (NSCLC).

Study Details

In the multicenter trial, 54 patients were randomly assigned between September 2014 and March 2019 to receive chemoradiotherapy, with or without consolidation chemotherapy, and with (n = 26) or without (n =28) metformin before the trial was closed early due to slow accrual. Chemoradiation therapy consisted of radiotherapy at 60 to 63 Gy in 30 daily fractions, with platinum-based therapy consisting of cisplatin/etoposide, cisplatin/vinorelbine, or carboplatin with either etoposide or paclitaxel. Metformin was given at 2,000 mg/d during chemoradiation therapy and for up to 12 months thereafter. The primary outcome was the proportion of patients with treatment failure, defined as locoregional disease progression, distant metastases, death, or discontinuation of trial treatment or planned evaluations for any reason within 12 months.

Treatment Failure Rates

Within 1 year, treatment failure occurred in 18 patients (69.2%) in the metformin group vs 12 (42.9%) in the control group (P = .05; difference = −26.4%, 95% confidence interval [CI] = −0.9% to −51.0%). 

KEY POINTS

  • The addition of metformin to chemoradiation was associated with poorer treatment outcomes.
  • Patients receiving metformin had higher rates of toxicity.

Progression-free survival at 1 year was 34.8% (95% CI = 16.6%–53.7%) in the metformin group vs 63.0% (95% CI = 42.1%–78.1%) in the control group (hazard ratio [HR] = 2.42, 95% CI = 1.14–5.10). Overall survival at 1 year was 47.4% (95% CI = 26.3%–65.9%) in the metformin group vs 85.2% (95% CI = 65.2%–94.2%) in the control group (HR = 3.80, 95% CI = 1.49–9.73).

Adverse Events

Grade ≥ 3 adverse events occurred in 53.8% of the metformin group vs 25.0% of the control group. The most common adverse events in the metformin group were lung infection (23.1% vs 0% in the control group), esophagitis (19.2% vs 3.6%), decreased lymphocytes (11.5% vs 3.6%), and decreased neutrophils (11.5% vs 0%).

The investigators concluded: “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. Metformin is not recommended in patients with locally advanced NSCLC who are candidates for chemoradiotherapy.”

Theodoros Tsakiridis, MD, PhD, of the Juravinski Cancer Centre at Hamilton Health Sciences, Ontario, is the corresponding author of the JAMA Oncology article.

Disclosure: This study was funded by a grant from the Canadian Institutes of Health Research. For full disclosures of the study authors, visit jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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