Novel Genomic Score Predicts Survival with Immune checkpoint inhibition in Neuroendocrine Neoplasms.

BACKGROUND: Immune checkpoint inhibition (ICI) has activity in Grade 3 (G3) neuroendocrine neoplasms (NENs), but predictive biomarkers of long-term overall survival (OS) are currently lacking. METHODS: We derived a genomic scoring system using a retrospective cohort of 54 NEN patients treated with nivolumab and/or ipilimumab, alongside a chemotherapy-only control (n = 15) and pan-cancer validation cohort (n = 1,661). An overall genomic score (GS-O) combining positive (GS-P) and negative response genes (GS-N) was calculated. RESULTS: In the ICI cohort, patients with GS-O ≥2 had significantly better outcomes: median OS was not reached, compared to 3.9 months for low scores (HR = 0.007, p < 0.001). After multivariate adjustment, GS-P was independently associated with improved OS while GS-N showed a trend towards worsened OS. Importantly, GS-O ≥2 did not predict survival in the chemotherapy-alone cohort but was validated as independently predictive in the pan-cancer validation dataset (HR = 0.92, p < 0.001). CONCLUSION: This study establishes a novel genomic score to predict OS in NENs treated with ICI with important pan-cancer implications.