18 F-BMS-986192 PET to Predict Durable Response to Nivolumab in NSCLC: A Novel Approach Beyond PD-L1 Immunohistochemistry

Programmed death ligand 1 (PD-L1) immunohistochemistry, the current standard biomarker for predicting response to programmed death protein 1/PD-L1 checkpoint inhibitors in non–small cell lung cancer, has moderate predictive value among others because of tumor heterogeneity and limited biopsy representation, whereas PD-L1 PET/CT using 18F-BMS-986192 enables noninvasive, whole-tumor assessment of PD-L1 expression and heterogeneity, potentially improving prediction of response to immunotherapy. Methods: In this prospective multicenter biomarker exploration study, patients with stage IV non–small cell lung cancer eligible for nivolumab-based therapies underwent baseline 18F-BMS-986192 PET/CT, 18F-FDG PET/CT, and tumor biopsy for PD-L1 immunohistochemistry before treatment initiation. The primary endpoint was durable clinical benefit, defined as progression-free survival (PFS) of 9 mo or greater, with secondary analyses assessing associations among tracer uptake, PD-L1 expression, survival outcomes, and PET-based radiomic features. Results: Of 91 enrolled patients, 77 were included in the final analysis of 18F-BMS-986192 PET/CT. Although PD-L1 immunohistochemistry did not differ between patients with PFS of less than 9 mo versus 9 mo or greater, PD-L1 PET uptake in lung lesions was significantly higher in patients with PFS of at least 9 mo (P = 0.01). Using an optimal mean SUVpeak cutoff of 2.4, PD-L1 PET demonstrated a high negative predictive value (94%) for durable clinical benefit, with significant associations for both PFS and overall survival, particularly in patients receiving first-line treatment. Tracer uptake showed no correlation with 18F-FDG uptake. Conclusion:18F-BMS-986192 PET/CT revealed interpatient PD-L1 variability. Low uptake in lung lesions predicted poor outcomes with high negative predictive value. 18F-BMS-986192 PET/CT demonstrated stronger negative predictive value than did baseline PD-L1 immunohistochemistry in this cohort. These findings require prospective validation.