Metformin Increases Glucose Uptake in Early-Stage NSCLC

Metformin appeared to increase glucose uptake in lung cancer cells, according to results from a phase II trial presented at the International Association for the Study of Lung Cancer (IASLC) 2019 North America Conference on Lung Cancer.

The hypothesis, borne out of many previous analyses and observations among diabetes patients, did not bear out in the data of the study, said lead author Stephen Chun, MD, from the division of radiation oncology at The University of Texas MD Anderson Cancer Center, in an interview with CancerNetwork. 

“This kind of flew in the face of all the preclinical modeling that we have, suggesting that it would suppress glucose uptake,” he said. “This is the opposite of what we thought… This really challenges the potential use of metformin as an antic-cancer therapy.” 

The single-blinded phase II trial included a group of 15 patients with inoperable, early-stage NSCLC – 60% with adenocarcinoma, 33.3% with squamous cell carcinoma, and 6.7% with carcinomas that were poorly differentiated. 

For 3 to 4 weeks, the patients were administered metformin (n = 14) or placebo (n = 1).

Observations were made with PET scans at baseline, mid-treatment (at 2 weeks), and also 6 months after radiation. Stereotactic body radiotherapy (SBRT) was measured at 50 grays (Gy) in 4 fractions used for peripheral tumors, and 70 Gy elsewhere.

More than half of patients randomized to metformin met PERCIST criteria for metabolic response at the mid-treatment point PET scan (57%); and 75% of those patients at that point showed progressive metabolic disease and 25% had partial metabolic response. 

The single placebo patient, at the same point, showed stable metabolic disease.

At the 6-month point, those treated with metformin showed a 69% complete metabolic response, 23% partial metabolic response, and 1 case of progressive metabolic disease. The patient on placebo, at the same 6-month mark, had complete metabolic response. 

Chun noted that this study offers further evidence backing a previous phase III study involving cancer outcomes with metformin that was presented at the 2019 American Society of Clinical Oncology Annual Meeting. 

“This provides further evidence that we should really be re-thinking whether there is any utility of metformin in lung cancer… and it may, in fact, be detrimental,” said Chun. 

But the results also further underscore the value of thorough scientific testing and observation, he added. 

“The most important lesson here is, this is why you have to do a clinical trial,” he said. “All the retrospective analyses, all the preclinical work was pointing in one direction – and then you do a prospective trial, and truth just stares you in the face.” 

References:

Chun S, Liao Z, Jeter M, et al. Metabolic Responses to Metformin in Early-Stage NSCLC Treated with Definitive Radiotherapy: Results of a Phase II Trial. Presented at: IASLC 2019 North America Conference on Lung Cancer; October 11, 2019; Chicago, Ill. Absract P1.20.