The potential adjunctive benefit of adding metformin to standard treatment in inoperable cancer patients: a meta-analysis of randomized controlled trials

BACKGROUND: Recently, there have been several randomized clinical trials (RCTs) conducted to evaluate the efficacy and safety of metformin plus standard treatment in inoperable cancer patients. Our meta-analysis aimed to assess the efficacy of metformin in combination with standard treatment in inoperable cancer patients. METHODS: PubMed and Embase databases were systematically searched for relevant RCTs investigating the efficacy of adding metformin to standard treatment for cancer patients. The pooled relative risk (RR) for tumor response and safety was calculated to assess the efficacy of combining metformin with standard treatment. Meta-analysis was subsequently performed to pool the hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS). RESULTS: Ten RCTs comprising 1033 patients were included in our current meta-analysis. In patients with breast cancer, results of meta-analysis showed that the addition of metformin to standard treatment was beneficial to objective response rate (ORR) with 30.3% (33/109) in the metformin plus standard treatment group and 16.1% (18/112) in the placebo group (RR 1.92, 95% CI: 1.19–3.10, P=0.008). OS and PFS were not significantly improved in patients who received metformin plus standard treatment compared with those who received placebo plus standard treatment (OS: HR 1.02, 95% CI: 0.71–1.46, P=0.916; PFS: HR 1.14, 95% CI: 0.86–1.50, P=0.366). For lung cancer patients, meta-analysis results showed adding metformin to standard treatment could benefit ORR (metformin 65.3% vs. placebo 54.6%, RR 1.22, 95% CI: 1.03–1.43, P=0.018) with no significant survival benefit in the metformin group. For patients with pancreatic cancer, the pooled ORR was 17.6% (16/91) in metformin plus standard treatment group and 20% (18/90) in the placebo group, indicating metformin did not benefit ORR (RR 0.85, 95% CI: 0.49–1.49, P=0.576). Besides, the addition of metformin to standard treatment did not increase the incidence rate of adverse effects. CONCLUSIONS: Our results indicated that addition of metformin to standard treatment was beneficial to ORR in inoperable breast or lung cancer patients without increasing the incidence of adverse effects. However, adding metformin to standard treatment could not benefit OS and PFS.