2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Time: Sunday June 2, 8:00 AM to 11:00 AM
Location: Hall A
Combination of metformin and gefitinib as first-line therapy for nondiabetic advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations: A multicenter, randomized, double-blind, placebo-controlled phase II trial.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #358)
J Clin Oncol 37, 2019 (suppl; abstr 9035)
Author(s): Yong He, Li Li, Liyan Jiang, Yubo Wang, Yizhuo Zhao, Xiaoju Zhang, Guoming Wu, Xiangdong Zhou, Jianguo Sun, Jun Bai, Biyong Ren, Kun Tian, Zhi Xu, Hualiang Xiao, Qi Zhou, Rui Han, Hengyi Chen, Haidong Wang, Zhenzhou Yang, Chan Gao; Department of Respiratory Medicine, Daping Hospital, Army Medical University, Chongqing, China; Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China; Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China; Department of Pulmonary Medicine, People's Hospital of Henan Province, Zhengzhou, China; Institute of Respiratory Disease, Xinqiao Hospital, Army Medical University, Chongqing, China; First Affiliated Hospital of Third Military University, Chongqing, China; Cancer Institute, Xinqiao Hospital, Army Medical University, Chongqing, China; Department of Medical Oncology, Shanxi Provincial People's Hospital, Xi'an, China; Cancer Center, Chongqing Three Gorges Central Hospital, Chongqing, China; Depantment of Respiration, General Hospital of Chengdu Military Command, Chengdu, China; Department of Pathology, Daping Hospital, Army Medical University, Chongqing, China; Department of Oncology, Fuling Center Hospital, Chongqing, China; Cardiothoracic Surgery Department, Southwest Hospital, Army Medical University, Chongqing, China; Cancer Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China; The Medical Department, 3D Medicines Inc., Shanghai, China
Background: Several lines of evidence suggested a role for metformin in sensitizing diabetic NSCLC patients to EGFR tyrosine kinase inhibitors (TKIs). However, data regarding its effects on non-diabetic populations remained scarce. We hereby examined metformin’s first-line use alongside gefitinib in EGFR mutation positive (EGFRm) patients without diabetes. Methods: In this trial (NCT01864681), 224 non-diabetic patients with treatment naïve stage IIIB-IV EGFRm NSCLC were randomly assigned at 1:1 to receive gefitinib plus metformin or placebo. Gefitinib was administered at 250 mg once daily, while metformin/placebo was initiated at 500 mg once daily and then escalated to 1000 mg twice daily over 2 weeks. Dose reduction was permitted for metformin/placebo in case of intolerable toxicity. The primary endpoint was progression-free survival (PFS) rate at 1 year. Secondary endpoints were overall survival (OS), PFS, objective response rate (ORR), and safety. Serum levels of interleukin-6 were also subjected to exploratory analysis. Results: Baseline characteristics were well balanced between treatment groups. The median duration of follow-up was 19.15 (IQR 12.99-28.44) months. The estimated 1-year PFS rate was 41.2% (95% confidence interval [CI] 30.0-52.2) in the metformin group versus 42.9% (95% CI 32.6-52.7) in the placebo group (p = 0.6268). Metformin did not increase median PFS (10.3 months vs. 11.4 months), median OS (22.0 months vs. 27.5 months), or ORR (66.0% vs. 66.7%) over placebo. No significant treatment group differences in terms of PFS were detected across subgroups either, including those with elevated levels of interleukin-6. Metformin plus gefitinib shared a similar safety profile with the control group, except for a remarkably higher incidence of diarrhea (78.38% vs. 43.24%). Conclusions: Our study did not show enhanced gefitinib efficacy upon addition of metformin and hence does not support its concurrent use with first-line EGFR-TKI therapy in non-diabetic EGFRm NSCLC patients. Clinical trial information: NCT01864681