Chicago, Illinois—Study findings presented at the 2019 ASCO Annual Meeting show that daily administration of oral metformin in combination with chemoradiotherapy (CRT) for locally advanced non–small-cell lung cancer (NSCLC) was well-tolerated, but that the metformin did not lead to an improvement in survival, nor did it affect rates of local-regional failure or distant metastasis.

“Metformin, a diabetes agent that inhibits mitochondria complex I, enhances radiotherapy and chemotherapy responses in pre-clinical models of NSCLC. NRG-LU001 examined whether metformin can improve outcomes of curative CRT in locally advanced [NSCLC],” explained Theodoros Tsakiridis, BSc, MSc, PhD, MD, FRCPC, Associate Professor, Department of Oncology, Division of Radiation Oncology, Juravinski Cancer Center, McMaster University, Hamilton, Ontario, Canada, and colleagues.

Seeking to determine the primary end point of 1-year progression free survival (PFS), Dr Tsakiridis et al recruited 170 nondiabetic patients with unresected, stage IIIA/B NSCLC between August 2014 and December 2016.

Patients were randomized in a 1:1 ratio to receive carboplatin-paclitaxel chemotherapy with concurrent chest radiotherapy (60 Gy) followed by consolidation carboplatin-paclitaxel chemotherapy or the same plus metformin (2000 mg daily) during cytotoxic therapy (control arm vs metformin arm, respectively).

The PFS and overall survival (OS) were estimated through the use of the Kaplan-Meier method, and the investigators used the cumulative incidence method to estimate time to local-regional progression (TTLRP) and time to distant metastasis (TTDM).

Dr Tsakiridis and his co-investigators planned to conduct their analysis at 102 PFS events, which ended up being in February 2019.

“There was no significant difference in rates or grade of toxicity between the two arms,” they reported.

The rates of PFS in the control arm at 1 and 2 years were 60.4% (95% CI, 48.5-70.4) and 40.1% (95% CI, 29.0-51.0), respectively, versus 51.3% (95% CI, 39.8-61.7) and 34.5% (95% CI, 24.2-45.1) in the metformin arm, respectively (multivariable Cox proportional hazard ratio [HR], 1.20; 95% CI, 0.81-1.78; P = .36).

The 2-year OS was 65.4% (95% CI, 53.5-75.0) versus 64.9% (95% CI, 53.1-74.5) in the control and metformin arms, respectively (HR, 1.03; 95% CI, 0.64-1.68); deaths due to disease occurred in 90% and 71% of each arm, respectively.

Of note, there were no significant differences found for TTLRP or TTDM.

“NRG-LU001 center reported outcomes show that oral daily metformin was well-tolerated in combination with CRT treatment for LA-NSCLC. However, metformin did not improve PFS and OS and did not alter the rates of local-regional failure or distant metastasis,” Dr Tsakiridis and colleagues concluded.—Hina Khaliq

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: the 2019 ASCO Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 8502.