The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

According to the results of a randomized study presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, the addition of metformin to curative chemoradiation therapy did not improve progression-free survival (PFS) or overall survival (OS) in patients with locally advanced, unresected non-small cell lung cancer (NSCLC).¹

Metformin is a medication typically used to treat diabetes, and is involved in the inhibition of mitochondrial respiration (although its mechanism of action is not fully understood). Results of retrospective studies have suggested that its use is associated with improved response rates in patients with cancer receiving radiation therapy.²

In the open-label, randomized NRG-LU001 study (ClinicalTrials.gov Identifier: NCT02186847) — a phase 2 trial of patients with stage IIIA/B unresected NSCLC —patients without diabetes were randomly assigned in a 1:1 ratio to receive chest radiation therapy (60Gy) with concurrent administration of carboplatin/paclitaxel combination chemotherapy followed by carboplatin/paclitaxel chemotherapy, with or without metformin hydrochloride (2000 mg orally daily) administered before and during chemoradiation, as well as during consolidation chemotherapy. The primary end point of the study was PFS; OS was a secondary end point.   

Of the 170 patients enrolled in the study, 84 and 86 were randomly assigned to the metformin and control arms, respectively. With respect to toxicity, there were similar rates of gastrointestinal, respiratory, vascular, and metabolic adverse events in the 2 study arms. However, only 39% of patients in the metformin arm completed metformin treatment as described in the study protocol; many of the remaining patients required a dose modification.

No significant differences in PFS were observed in the intention to treat (ITT) population of patients between the 2 study arms (hazard ratio [HR], 1.15; P =.2441). In an unplanned, post-hoc analysis including patients who completed treatment according to protocol, median PFS was 15.4 months and 16.6 months for those receiving metformin versus those who did not, respectively. Similarly, there was no significant difference in OS between the 2 study arms in the ITT population, although the 2-year OS rate of 65.4% was higher than expected for this population.

While cancer-specific mortality was 90% for patients in the control group, 71% of the deaths in the metformin-treated patients were attributed to disease.

In conclusion, the study presenter noted that, while well tolerated, metformin did not improve PFS or OS, and did not alter the rates of local-regional failure or distant metastasis, in patients with NSCLC.

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.

References

1. Tsakiridis T, Hu C, Skinner HD, et al. Initial reporting of NRG-LU001 (NCT02186847), randomized phase II trial of concurrent chemoradiotherapy (CRT) +/- metformin in locally advanced non-small cell lung cancer (NSCLC). Presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 3, 2019; Chicago, IL. Abstract 8502.
2. Samsuri NAB, Leech M, Marignol L. Metformin and improved treatment outcomes in radiation therapy – a review. Cancer Treat Rev. 2017;55:150-162.