Improved progression free survival for patients with diabetes and locally advanced non-small cell lung cancer (NSCLC) using metformin during concurrent chemoradiotherapy

Wink, Krista C.J.; Belderbos, J.; Dieleman, Edith; Rossi, Maddalena; Rasch, Coen R. N.; Damhuis, Ronald; Houben, Ruud; Troost, Esther G.C.

doi:10.1016/j.radonc.2016.01.012

Cited by 67 publications

(55 citation statements)

References 43 publications

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“…We found that the metformin use was associated with a lower risk of lung cancer-specific mortality (HR 0.82, 95% CI 0.73−0.92, p < 0.001) and with a lower risk of death from all causes (HR 0.83, 95% CI 0.7−0.92, p = 0.001). Several studies reported similar findings to our study [16,20,[32][33][34][35][36][37][38][39][40].…”

Section: Discussionsupporting

confidence: 91%

A Cohort Study of Exposure to Antihyperglycemic Therapy and Survival in Patients with Lung Cancer

Danila

Linkeviciute-Ulinskiene

Zablockis

et al. 2020

IJERPH

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We evaluated the effect of antihyperglycemic therapy on the survival of patients with lung cancer (LC). The analysis included patients with LC and concomitant type 2 diabetes. 15,929 patients were classified into five groups: metformin users, insulin users, metformin and insulin users, sulphonylurea users and non-diabetic group. A multivariate analysis showed that exposure to either metformin or to insulin was associated with a lower risk of LC-specific mortality, and this approached statistical significance (HR 0.82, 95% CI 0.72-92 for metformin and HR 0.65, 95% CI 0.44-95 for insulin). When deaths from all causes were considered, only metformin exposure was associated with a significantly lower risk of death (HR 0.82, 95% CI 0.73-0.92). Users of sulphonylurea were at a higher risk of LC-specific and overall mortality (HRs 1.19, 95% CI 0.99-1.43 and 1.22, 95% CI 1.03-1.45). Our study shows a positive effect of metformin on the survival of patients with LC. Moreover, our results show that exposure to insulin was associated with a lower risk of LC-specific mortality, but not with deaths from all causes. The study results suggested that users of sulphonylurea may be at a higher risk of LC-specific and overall mortality.

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Section: Discussionsupporting

confidence: 91%

A Cohort Study of Exposure to Antihyperglycemic Therapy and Survival in Patients with Lung Cancer

Danila

Linkeviciute-Ulinskiene

Zablockis

et al. 2020

IJERPH

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“…All the included studies were reported in English. Of the 10 articles [17–19, 21–27], 1 described case-control design and 5 described cohort design involved Western region, and 4 described cohort design involved Asian region. Moreover, there were two publications focusing on SCLC, five on NSCLC, one on mixed cancers including SCLC and NSCLC, and two with unavailable information concerned.…”

Section: Resultsmentioning

confidence: 99%

Metformin therapy associated with survival benefit in lung cancer patients with diabetes

Wan

Chen

et al. 2016

Oncotarget

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The purpose of this study is to summarize the currently available evidence regarding the concerned issue by performing a comprehensive meta-analysis. Relevant publications reporting the association of metformin use with survival of lung cancer patients with diabetes were electronically searched to identify eligible studies. The meta-analysis was performed with hazard ratios (HRs) and 95% confidence intervals (95% CIs) as effect measures for disease-free survival(DFS) and overall survival(OS) estimates. A total of 17 individual studies from 10 publications were included in the meta-analysis. Overall, the results revealed a significant association of metformin use with a better survival of lung cancer patients with diabetes(for DFS: HR = 0.65, 95%CI = 0.52-0.83; for OS: HR = 0.78, 95%CI = 0.64-0.93). The subgroup analyses showed similar association in Asian region(for DFS:HR = 0.69, 95%CI = 0.59-0.80; for OS: HR = 0.55, 95%CI = 0.46-0.67) but not in Western region. Such association was also presented in small cell lung cancer (for DFS: HR = 0.54, 95%CI = 0.38-0.77; for OS: HR = 0.52, 95%CI = 0.39-0.69) and in non-small cell lung cancer(for DFS: HR = 0.70, 95%CI = 0.51-0.96; for OS: HR = 0.75, 95%CI = 0.58-0.97). Analyses stratified by treatment strategy showed a reduction in the risk of cancer-related mortality in patients receiving chemotherapy(for DFS: HR = 0.71, 95%CI = 0.64-0.83; for OS: HR = 0.58, 95%CI = 0.47-0.71) but not in patients receiving chemoradiotherapy. The meta-analysis demonstrated that metformin use was significantly associated with a favorable survival outcome of lung cancer patients with diabetes.

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“…Similar retrospective analysis of Surveillance, Epidemiology, and End Results data, metformin was found to significantly improve survival (hazard ratio 0.80, 95% confidence interval [CI]: 0.71-0.89) in metastatic NSCLC patients with diabetes even after adjusting for demographics, diabetes severity and treatment, cancer characteristics, and oncologic treatment [9]. In a second retrospective study of diabetic patients on metformin therapy with locally advanced NSCLC who received concurrent chemoradiotherapy, median PFS (41 vs. 15 months) and 2-year distant metastasis-free survival (74% vs. 53%) was significantly improved, although no difference in overall survival (OS) was found [10]. Collectively, these retrospective studies suggest that metformin has anticancer effects and that tight glucose control alone is not the only, or even primary, mechanism by which metformin exerts these effects.…”

Section: Introductionmentioning

confidence: 99%

A Randomized Phase II Study of Metformin plus Paclitaxel/Carboplatin/Bevacizumab in Patients with Chemotherapy-Naïve Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer

et al. 2018

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The anticancer effects of metformin continue to be elucidated. To the authors' knowledge, this is the first trial in nondiabetic advanced non-small cell lung cancer patients to show a significant change in outcome with the addition of metformin to standard first-line chemotherapy. Well tolerated and widely available, metformin is a drug that should be considered for further study in the lung cancer treatment landscape.

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Improved progression free survival for patients with diabetes and locally advanced non-small cell lung cancer (NSCLC) using metformin during concurrent chemoradiotherapy

Cited by 67 publications

References 43 publications

A Cohort Study of Exposure to Antihyperglycemic Therapy and Survival in Patients with Lung Cancer

A Cohort Study of Exposure to Antihyperglycemic Therapy and Survival in Patients with Lung Cancer

Metformin therapy associated with survival benefit in lung cancer patients with diabetes

A Randomized Phase II Study of Metformin plus Paclitaxel/Carboplatin/Bevacizumab in Patients with Chemotherapy-Naïve Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer

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