Immunomodulatory Effect of First-Line Cisplatin Versus Carboplatin in Response to Second-Line Nivolumab Therapy in Metastatic Non-Small Cell Lung Cancer.

[BACKGROUND] Non-small cell lung cancer (NSCLC) treatment often involves a combination of first-line immunotherapy (IO) and chemotherapy, with platinum-based regimens as alternatives. Nivolumab monotherapy is a widely used second-line treatment post-platinum chemotherapy. This is the first study to explore the immunomodulatory effects of cisplatin in advanced NSCLC patients receiving nivolumab.

[METHODS] This retrospective study included 186 metastatic NSCLC patients from four centers in Turkey. All patients received nivolumab after progression on platinum-based chemotherapy. Multivariate Cox regression was performed to identify independent prognostic factors for progression-free survival (PFS) and overall survival (OS).

[RESULTS] Patients treated with cisplatin-based chemotherapy ( = 91) had significantly longer median PFS (7.2 months vs. 4.9 months,  = 0.034) and OS (16.0 months vs. 9.9 months,  = 0.014) compared to those treated with carboplatin ( = 95). Cisplatin-based chemotherapy and ECOG performance status were identified as independent prognostic factors for both PFS and OS.

[CONCLUSION] This study highlights the potential immunomodulatory effects of cisplatin, demonstrating improved survival outcomes in NSCLC patients treated with nivolumab. Specifically, our results reveal cisplatin's unique capacity to modulate the tumor microenvironment, offering a novel avenue for optimizing checkpoint inhibitor therapy. These findings underscore the importance of platinum selection in enhancing immunotherapy efficacy and provide a basis for prospective studies to refine clinical guidelines.