A large number of studies in recent years has shown that the cancer incidence of diabetes patients who take metformin has been quite low, and metformin is associated with the decline of cancer mortality compared to insulin and sulfonylureas for diabetes; for lung cancer patients, the survival of patients with stage IV lung cancer complicated with diabetes has been significantly increased after taking metformin.
Then, can cancer patients without diabetes delay the targeted drug resistance and prolong PFS (progression-free survival) and OS (overall survival) by taking metformin? There have been many studies on metformin at the ASCO Meeting this year. Let’s check the study results below.
1. Combination of metformin and gefitinib could not improve the PFS or OS of nondiabetic advanced NSCLC patients
According to the basic research, metformin can strengthen the efficacy of EGFR-TKI, however, this has not been proved by clinical trials. In view of this, researchers from Daping Hospital of China have conducted a multicenter, double-blind, placebo-controlled Phase II clinical study, and the results have been announced at the 2019 ASCO Meeting.
The study enrolled previously untreated 224 patients with stage IIIb or IV NSCLC and EGFR mutation, who were randomly assigned to the group receiving 250mg gefitinib (oral, once daily) plus 500mg metformin (oral, once weekly) or the group receiving the said gefitinib plus placebo, with metformin escalated to 1,000mg (oral, twice daily) 2 weeks later. The primary endpoint was PFS rate at 1 year, and the secondary endpoints were PFS, OS, ORR, and safety.
Baseline characteristics were well balanced between the two groups. The results showed that the PFS rate at 1 year was separately 41.2% and 42.9% in the metformin group and placebo group, with the difference not statistically significant (P=0.6268). The combination with metformin did not increase the PFS (10.3 months vs. 11.4 months), OS (22.0 months vs. 27.5 months), or ORR (66.0% vs. 66.7%) over placebo. No survival advantages of the combination with metformin were detected across subgroups either. The two groups had similar adverse reactions, except for a remarkably higher incidence of diarrhea in the placebo group (78.38% vs. 43.24%).
Therefore, researchers held that the combination with metformin could not improve the prognosis of nondiabetic advanced NSCLC patients with EGFR mutation after receiving TKI therapies.
2. Combination of metformin and concurrent chemoradiotherapy did not lead to survival benefits
Professor Theodoros Tsakiridis from Canada Juravinski Cancer Center led the NRG-LU001 Phase II study to assess whether metformin can improve the efficacy of radical concurrent chemoradiotherapy in stage ⅢA/ⅢB NSCLC not complicated with diabetes.
The enrolled 170 patients were randomized 1:1 to either carboplatin-paclitaxel chemotherapy concurrent with chest RT (60Gy), followed by consolidation carboplatin-paclitaxel chemotherapy (Control Arm) or the same and metformin (2,000mg/d) during chemotherapy therapy (Experimental Arm) between Apr. 2014 and Dec. 2016.
According to the study results, 1- and 2-year PFS was 60.4% and 40.1% in the Control Arm vs. 51.3% and 34.5% in the Metformin Arm, with the difference not statistically significant. OS at 2 years was 65.4% for the Control Arm and 64.9% for the Metformin Arm, both of which were close.
The combination of metformin and concurrent chemoradiotherapy for locally advanced NSCLC was well-tolerated, however, metformin did not improve patients’ PFS or OS and did not alter the rates of local-regional failure or distant metastasis.
3. Metformin could not bring benefits to prostate cancer patients
TAXOMET, a prospective multicenter randomized controlled Phase II study, was conducted to compare docetaxel plus metformin versus docetaxel plus placebo in metastatic castration-resistant prostate cancer (mCRPC), with the primary endpoint being PFS response rate (≥50% decrease) and secondary endpoints including objective response rate (ORR), PFS, OS, toxicity, and quality of life (QoL). The stu...
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