A retrospective study suggested that patients with locally advanced non-small cell lung cancer (NSCLC) who were taking metformin for diabetes at the time of cancer treatment faced a lower risk of developing metastatic disease.1 But while some other retrospective studies have come to similar conclusions, others have not—and prospective clinical trials are underway to explore metformin’s anti-cancer potential.

“Lung cancer is, despite all efforts, still one of the most fatal cancers in the world, with most patients being diagnosed with NSCLC,” noted the study’s senior author, Esther G.C. Troost, MD, PhD, senior radiation oncologist at the University Hospital Carl Gustav Carus in Dresden, Germany, and professor of image-guided high precision radiation therapy.

Some observational and retrospective analyses have shown that patients with diabetes might sometimes have a better prognosis than other patients, and recent epidemiological studies have tied both reduced cancer risks and improved cancer-treatment outcomes, to patients’ use of metformin, a well-tolerated and widely prescribed medication for type-2 diabetes.

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In an attempt to “unravel the mechanisms or treatment modalities” that might improve survival for stage III NSCLC patients, Professor Troost teamed up with lead study author Krista C.J. Wink, MD, and colleagues in the Netherlands to retrospectively analyze data for 682 patients with NSCLC (59 metformin users and 623 matched controls) who underwent chemoradiotherapy with curative intent.1 Using a large multicenter cohort dataset, they studied the influence of metformin use on locoregional recurrence-free survival, progression-free survival (PFS), distant metastasis-free survival (DMFS), and overall survival (OS).

“In the multivariate analysis of all 682 included patients, we found that gender and WHO performance score were significantly correlated with overall survival,” Professor Troost told Cancer Therapy Advisor. “Moreover, DMFS and PFS were statistically significantly longer in the patients using metformin.”

For DMFS, metformin use was associated with 74% at 2 years, versus 53% among controls (P = .01); 2-year PFS was 58% vs 37%; median PFS was 41 months for metformin users vs 15 months (P = .01).1 No difference was found for OS.

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The addition of metformin to concurrent chemoradiotherapy in patients with stage III NSCLC “may improve cancer-related outcome,” Professor Troost said. “However, this needs confirmation in a prospective clinical trial, such as the phase 2 [ALMERA] clinical trial that is already planned by the Ontario Clinical Oncology Group (NCT02115464).”

“This is an interesting and thought-provoking study,” commented Roy Decker, MD, PhD, associate professor and clinical research program leader in therapeutic radiology, and director of the Thoracic/Stereotactic Body Radiotherapy Program at the Yale Cancer Center in New Haven, CT. “This suggests that metformin may have prevented the spread of the cancer in some patients.”