e21585 Background: Despite efficacy of human checkpoint inhibitors, only 20 to 30% of treated patients present long term benefits. Circadian variations of the delivery of nivolumab to patients with advanced non-small-cell lung cancer (NSCLC) are proposed here as a factor potentially influencing the efficacy. Methods: A total of 1318 courses of nivolumab were administered in 57 consecutive patients with advanced NSCLC from September 2015 to December 2019 in Medical Oncology Unit of Montfermeil hospital. Percentage of total dose per patient delivered before and after 12:00 pm was computed and corelated to objective response rate (ORR), progression free survival (PFS) and overall survival (OS). Results: Twenty eight patients (49%) received ≥ 50% of their treatment before 12:00 pm (morning group) and 29 patients (51%) after 12:00 pm (afternoon group). ORR was 53.6% in morning group and 31.0% in afternoon group; p = 0.083. Both PFS and OS were significantly longer in morning group as compared to afternoon group. Median PFS was 18.6 months [95%CL, 8.6 – 28.7] and 3.5 months [2.9 – 4.1] in morning and afternoon group respectively; p < 0.001. After a maximum follow-up of 48 months, median OS was not reached in morning group whereas it was 14.4 months [0.0 – 29.5] in afternoon group; p = 0.004. Conclusions: The significant difference in the efficacy of nivolumab between morning and afternoon group is indirect evidence of the influence of circadian rhythm on the metabolism of this checkpoint inhibitor. The application of this finding in clinical practice should allow an increase of nivolumab efficacy in patients with advanced NSCLC.

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