Addition of diabetes drug Metformin improves survival in lung cancer patients: JAMA Oncology

Mexico: The diabetes drug metformin apart from lowering blood sugar in type 2 diabetes patients has been previously shown to have varied benefit in other health conditions as well. Now, a recent study has shown benefit of the drug for lung cancer patients.

According to results of the phase 3 study, published in the JAMA Oncology journal, the addition of metformin in patients with EGFR (epidermal growth factor receptor)-mutated lung adenocarcinoma increased progression-free and overall survival sans any significant increase in adverse events.

Metformin hydrochloride is emerging as a repurpose anticancer drug. The drug has shown to improve outcomes across a wide variety of neoplasms, including lung cancer in preclinical and retrospective studies.

Oscar Arrieta, Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico, and colleagues assessed the progression-free survival in patients with advanced lung adenocarcinoma who received EGFR–TKIs (tyrosine kinase inhibitors) therapy plus metformin compared to those who received EGFR-TKIs alone.

In the study, 139 patients (Mean age: 59.4 and 65.5% were female) were randomized to receive standard EGFR-TKIs (n=70) or EGFR-TKIs plus metformin 500 mg twice daily (n=69) from March 2016 to December 2017.

All the participants had histologically confirmed stage IIIb/IV lung adenocarcinoma with an activating EGFR mutation and measurable lesions. All were naïve to EGFR-TKIs, had an Eastern Cooperative Oncology Group performance status of 2 or less, and a life expectancy of at least 12 weeks. Median follow-up was 16.9 months.

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Key findings include:

• The median PFS was significantly longer in the EGFR-TKIs plus metformin group compared with the EGFR-TKIs group (13.1 months compared with 9.9 months).


• The median overall survival was also significantly longer for patients receiving combination therapy: 31.7 months vs 17.5 months.


• Patients allocated to receive added metformin were more likely to respond to EGFR-TKI therapy: 71.0% vs 54.3%.


• The combination lowered the risk of non-response, achieving an objective response rate of 0.48.


• The addition of metformin was the only factor independently associated with better overall survival, decreasing the risk of death by half.


• Grade 3/4 adverse events in both arms were similar in frequency in both arms and included diarrhoea, rash, nausea, and mucositis.

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"To our knowledge, this is the first study to prospectively show that the addition of metformin to standard EGFR-TKIs therapy in patients with advanced lung adenocarcinoma significantly improves PFS. These results justify the design of phase 3, placebo-controlled study," wrote the authors.

To read the complete study log on to doi:10.1001/jamaoncol.2019.2553