Combination metformin and epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR-TKI) therapy improved progression-free survival in patients with EGFR-mutated lung adenocarcinoma, according to results from a phase 2 trial.
“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 [progression-free survival],” wrote Oscar Arrieta, MD, of the Instituto Nacional de Cancerología, Mexico, and colleagues in JAMA Oncology.
The open-label, randomized study included 139 patients, 69 of whom were randomly assigned to receive metformin plus EGFR-TKI therapy and 70 of whom received EGFR-TKI monotherapy.
EGFR-TKI therapy was selected based on physician choice and consisted of either afatinib dimaleate, gefitinib, or erlotinib hydrochloride at regular doses. Study patients in the combination arm received metformin 500 mg twice daily.
The primary endpoint was PFS (intent-to-treat population). Secondary endpoints included overall survival (OS), objective response rate, and safety.
After analysis, the researchers found that the median PFS was 13.1 months with metformin-EGFR-TKI combination therapy and 9.9 months with EGFR-TKI monotherapy (hazard ratio, 0.60; P = .03).
In addition, the median OS was also significantly prolonged for patients receiving combined treatment (31.7 months vs. 17.5 months; P = .02).
“Multivariable analysis showed that treatment with metformin is independently associated with longer PFS and OS,” the researchers wrote.
With respect to safety, no significant rise in adverse events was observed, and toxicities were comparable across both treatment groups.
The researchers acknowledged that a key limitation of the study was the absence of a double-blinded design. As a result, various biases could have influenced the results.
“The results from this phase 2 study warrant the design of a larger, phase 3, placebo-controlled study to draw more robust conclusions,” they said.
The study was funded by the National Council for Science and Technology in Mexico. The authors reported financial affiliations with AbbVie, AstraZeneca, Boehringer Ingelheim, Lilly, Bristol-Myers Squibb, Merck, Pfizer, Roche, and several others.
SOURCE: Arrieta O et al. JAMA Oncol. 2019 Sep 5. doi: 10.1001/jamaoncol.2019.2553.