Morphine and metformin impact immunotherapy benefit in patients with NSCLC: Results of the real-world study IFCT-1502 CLINIVO-SNDS

Background: Most patients with lung cancer have comorbidities at the time of diagnosis. Treatments prescribed for cancer-related symptoms are thus added to drugs for chronic diseases. The impact of comedication on immunotherapy efficacy has been studied in retrospective series, but the results are often biased by the lack of information on the independent prognostic impact of comedication weighted for comorbidities and disease aggressiveness. Methods: The IFCT-1502 CLINIVO study is a nationwide retrospective cohort of patients with advanced non-small cell lung cancer who received nivolumab in second or later lines of treatment as part of the French Expanded Access Program. We retrieved comedication prescriptions from 90 days before to 30 days after the first nivolumab administration via the French national healthcare database. We report the results of a comprehensive post hoc analysis investigating the impact of comedication on treatment response considering well-known negative prognostic factors. Results: We selected 753 patients whose medical and comedication records were available. According to the multivariate analysis, morphine and corticosteroids > 20 mg per day were associated with poor overall survival regardless of disease aggressiveness. Conversely, metformin was associated with better overall survival. Morphine and corticosteroids were also found to be associated with shorter real-world progression-free survival according to multivariate analysis, as were poor prognostic factors such as liver metastasis and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≥ 2. Conclusion: Our study confirmed the negative impact of morphine and high-dose corticosteroids on immunotherapy efficacy regardless of poor prognostic factors related to disease aggressiveness. On the other hand, our findings suggested a positive impact of metformin on immunotherapy outcomes.