Hematological Events in Metformin Treated NSCLC Patients Post Chemotherapy: Drug Repurposing Based on Real-World Evidence from Case Controlled Study

In this multi-center case controlled study aimed at metformin repurposing on the basis of survival benefit in non-small cell lung cancer patients compared to non-diabetic patients, based on hematological events mitigating ability of metformin induced by chemotherapy.

Methods

At the Severance hospitals from 1 ^st Jan 2010 to 1 ^st Jan 2020, (n = 1851) patients were identified from hospital database. Further analysis was performed using propensity score matched to analyze the survival outcome of metformin comparing with non-diabetic control group in non-small cell lung cancer patients. Using propensity score matching of 8 variables, post-chemotherapy days survived by diabetic patients compared with untreated patients shown in this study. Six different chemotherapy induced clinical events related to WBC, platelets, and neutrophils are studied to identify possible detrimental role of metformin post chemotherapy frequency/cycle stratification.

Results

Total 354/1851 patients identified as diabetic non-small cell lung cancer patients remaining were non-diabetic patients. Post-propensity score matching 354 non-diabetic patients survived 521 days (95% CI 459 – 582), compared to treatment group patients survived for 580 days (95% CI 508 – 651) non-significantly with ( p -value 0.1). The patients under radiotherapy survived 624 days (95% CI 521 – 726) in 142 control group, compared to that chemoradiation metformin treated patients (n = 136) survived 798 days (95% CI 698 – 967) p -value-0.02. Among (n = 136) chemoradiation metformin patients treated prior to 180 days of chemotherapy survived mean days post chemotherapy start 2-year hazard ratio 0.42 (95% CI 0.008 – 0.7) p- value 0.02 compared to patients received metformin 180 days post chemotherapy. Post propensity score matching Metformin treatment did not significantly reduce leukopenia, neutropenia, and thrombocytopenia events post chemotherapy compared to control ( p -value < 0.05). Further chemotherapy cycle stratification leukocytosis, neutrophilic leukocytosis, and thrombocytopenia events were significantly high ( p -value < 0.05) causing increased deaths in chemotherapy non-responder compared to responder group.

Conclusion

The overall survival of diabetic patients treated with metformin is not different from untreated patients. Fatalities in treatment and control groups induced by chemotherapy were similar. Prolonged use of metformin reduced hematological event risk in NSCLC patients.