For a study, scientists determined that as a standard procedure, oncologists prescribed systemic therapy with platinum-based doublet chemotherapy with or without bevacizumab to treat patients with advanced or metastatic non-small cell lung cancer. A targeted oncogenic driver mutation or high programmed death-ligand 1 expression remained unavailable. It caused the oncologists to continue with the treatment mentioned above. Metformin demonstrated antitumor effects through various insulin-dependent and insulin-independent mechanisms. It also exhibited potential as a synergist with chemotherapy. The researchers recruited patients with chemotherapy-naïve advanced or metastatic nonsquamous non-small-cell lung cancer in their open-label single-center phase II study (NCT01578551). They randomized the patients (3:1). Then, they administered the patients with carboplatin, paclitaxel, and bevacizumab with (Arm A), or without (Arm B) concurrent metformin for four to six cycles. Afterward, they followed the treatment by maintenance therapy with (bevacizumab ± metformin). The researchers continued the treatment until disease progression, intolerable toxicity, or study withdrawal. Thus, the principal result was 1-year progression-free survival (PFS). Secondary results included overall survival, response to therapy, and toxicity.

The researchers recruited 25 patients between August 2012 and April 2015. About 24 out of 25 patients received a minimum of one therapy cycle. The researchers stopped the investigation untimely because of slow accrual and alterations in standard first-line therapy of advanced non-small-cell lung cancer. The 1-year PFS on Arm A (n=18) was 47% (95% CI: 25%–88%), which surpassed the historical control 1-year PFS of 15%. And median overall survival of patients treated on Arm A was 15.9 months (95% CI: 8.4–not available [NA]) and 13.9 months (95% CI: 12.7–NA) on Arm B. The researchers did not notice any prominent changes in toxicity between the study arms.

The researchers believed that their investigation was the first to demonstrate the utilization of metformin brought notable benefits in PFS in the patient population. It also exhibited the effectiveness of metformin in treating advanced non-small cell lung cancer.