Early morning immune checkpoint blockade and overall survival of patients with metastatic cancer: An In-depth chronotherapeutic study

Introduction Recent retrospective studies suggest potential large patient's benefit through proper timing of immune checkpoint blockers (ICB). The association between ICB treatment timing and patient survival, neoplastic response and toxicities was investigated, together with interactions with performance status (PS) and sex. Methods A cohort of patients with metastatic or locally advanced solid tumors, who received pembrolizumab, nivolumab, atezolizumab, durvalumab, or avelumab, alone or with concomitant chemotherapy, between November 2015 and March 2021, at the Centre Leon Bérard (France), was retrospectively studied. Results 361 patients were investigated (80% non-small cell lung cancer patients, mean [SD] age: 63 [ 11 Giacchetti S. Bjarnason G. Garufi C. et al. Phase III trial comparing 4-day chronomodulated therapy versus 2-day conventional delivery of fluorouracil, leucovorin, and oxaliplatin as first-line chemotherapy of metastatic colorectal cancer: the European Organisation for Research and Treatment of Cancer Chronotherapy Group. J Clin Oncol Off J Am Soc Clin Oncol. 2006; 24: 3562-3569https://doi.org/10.1200/JCO.2006.06.1440 Crossref PubMed Scopus (178) Google Scholar ] years, 39% of women, 83% PS0-1 at first infusion, 19% received concomitant chemotherapy). ICB were administered from 07:25 to 17:21 and optimal morning/afternoon cut-off was 11:37. Morning infusions were associated with increased OS as compared to afternoon (median 30.3 vs 15.9 months, p=0.0024; HR 1.56 [1.17-2.1], p=0.003). A strong PS-timing interaction was found (PS0-1 patients, HR=1.53 [1.10-2.12], p=0.011; PS2-3 patients, HR=0.50 [0.25-0.97], p=0.042). 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Prospective randomized trials are needed to confirm this retrospective study.