Adding metformin to advanced lung cancer therapy may boost survival

By Marilynn Larkin

NEW YORK (Reuters Health) - 12/9/2019

Adding metformin to standard epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) therapy in patients with advanced lung cancer improved progression-free and overall survival in a phase 2 trial in Mexico.

"This study is an example of drug repurposing and represents a promising strategy for the use of licensed drugs for treating a wider array of medical conditions," Dr. Oscar Arrieta of Instituto Nacional de Cancerologia in Mexico City told Reuters Health.

"Patients who received metformin, a widely-used agent for the treatment of type-2 diabetes, in addition to standard targeted therapy agents for lung adenocarcinoma, had a significant increase in survival," he said by email.

"We are aware that there are novel agents which can also offer survival benefits," he added. "However, an important key point for metformin is its cost, at $0.03-0.80 USD per unit, this would represent a much more affordable option to improve patient outcomes, particularly in resource-limited settings."

As reported online September 5 in JAMA Oncology, Dr. Arrieta and colleagues randomized 139 patients with histologically confirmed stage IIIB-IV lung adenocarcinoma with an activating EGFR mutation to EGFR-TKIs (erlotinib, hydrochloride, afatinib dimaleate, or gefitinib at standard dosage) plus metformin hydrochloride (500mg twice a day) or EGFR-TKIs alone.

Patients' mean age was 59.4 and 65.5% were women.

Median progression-free survival was significantly longer in the EGFR-TKIs plus metformin group compared with the EGFR-TKIs alone group (13.1 vs. 9.9 months; hazard ratio, 0.60).

Similarly, median overall survival was also significantly longer for patients receiving the combination therapy (31.7 vs. 17.5 months).

Dr. Arrieta said, "We are currently undertaking a larger, Phase III trial in order to arrive at more robust conclusions. Meanwhile, we encourage clinicians and researchers to consider the possibility of establishing studies in their particular populations in order to add to the body of evidence."

"Clinical advice should always be based on the highest available medical evidence, in order to offer our patients the best available care," he added. "It is also important to always be aware of limitations - including financial limitations - to accessing therapy and therefore explore options which can overcome such drawbacks in patient care."

Dr. Ravi Salgia, Chair and Professor, Department of Medical Oncology and Therapeutics Research, City of Hope in Duarte, California, commented by email, "This is an important phase II randomized study (with) significant potential implications for mechanisms of tumor shrinkage and relationship to metabolism."

"It will be crucial to do a double-blinded study as well as use newer EGFR-TKI agents such as osimertinib," he told Reuters Health. "Also, it will be important to know which EGFR mutations are more sensitive."

Dr. Arrieta also pointed out, "This is one of the scant independent clinical studies conducted in Mexico, and its results should encourage future government-funding of relevant studies for pressing public health issues."


JAMA Oncol 2019.

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