The addition of metformin to chemoradiation may not be warranted in locally advanced NSCLC, according to results from a phase 2 study in JAMA Oncology. 

The open-label trial from August 2014 to December 2016 studied 170 patients with unresectable stage-III NSCLC without diabetes, across 79 institutions in the US, Canada, and Israel. 

Patients were randomized to one of two treatment regimens: concurrent 60 Gy radiation with weekly carboplatin and paclitaxel chemotherapy, followed by two cycles of consolidative chemotherapy every 3 weeks; or 2000 mg daily metformin added to concurrent radiation and consolidative chemotherapy. 

A total of 167 patients were included in the final analysis (median age 64 years; 97 men; 137 White). Of these, 81 individuals underwent chemoradiation and consolidation chemotherapy, while 86 received metformin plus chemoradiation. 

The trial’s primary endpoint was one-year PFS. Secondary outcome measures included overall survival, time to local-regional recurrence, time to distant metastasis, and toxicity. 

Over a median follow-up period of 27.7 months among living patients, the researchers found that one-year PFS rates were 60.4% among patients in the chemoradiation group, compared with 51.3% among their counterparts who received metformin (hazard ratio 1.15; p=0.24).  

On multivariate analysis, clinical stage was the only factor significantly associated with PFS (HR 1.79; p=0.005).  

None of the remaining variables were significantly associated with PFS. This included treatment group (HR 1.20; p=0.36), histology (HR 1.24; p=0.30), and Zubrod performance status (HR 0.70; p=0.09). 

In the intention-to-treat analysis, OS at one year was also similar between groups: 80.2% in the chemoradiation group and 80.8% in the metformin group. There were no significant differences in local-regional recurrence or distant metastasis at either one or two years.  

The two groups also proved comparable with respect to adverse events, according to the researchers.  

Although the addition of metformin to chemoradiation did not add toxic effects to patients with locally advanced NSCLC, it also did not confer any type of survival benefit in this patient population.  

“It is still uncertain whether metformin will have a use in the management of lung cancer in the future,” according to lead author Heath Skinner, MD, PhD, UPMC Hillman Cancer Center in Pittsburgh; NRG Oncology Statistics and Data Management Center, Philadelphia; Johns Hopkins School of Medicine, Baltimore. 


By Michael Vlessides, /alert Contributor