Effect of time‐of‐day nivolumab and stereotactic body radiotherapy in metastatic head and neck squamous cell carcinoma: A secondary analysis of a prospective randomized trial

Abstract Background Prior work documented circadian rhythm impacts on efficacy and toxicity of cancer therapies. Methods Secondary analysis of prospective, phase II trial of metastatic HNSCC randomized to nivolumab+/−SBRT. Used cutoffs of 1100 and 1630. Timing classified by first infusion or majority of SBRT (e.g., PM SBRT defined by two or three fractions after 1630). Results Of 62 patients, there was no significant difference in median PFS between AM nivolumab ( n = 7, 175 days), PM nivolumab ( n = 21, 58 days), or Mid‐Day nivolumab ( n = 34, 67 days; p = 0.8). There was no significant difference in median PFS with AM SBRT ( n = 4, 78 days), PM SBRT ( n = 13, 111 days), or Mid‐Day SBRT ( n = 15, 63 days; p = 0.8). There was no significant difference in Grade 3–4 toxicity or ORR. Sensitivity analyses with other timepoints were negative. Conclusions Further work may elucidate circadian impacts on select patients, tumors, and therapies; however, we found no significant effect in this study.