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.

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.

背景 先前的研究记录了昼夜节律对癌症治疗的疗效和毒性的影响。 方法 对一项前瞻性Ⅱ期转移性头颈部鳞状细胞癌（HNSCC）试验进行二次分析，该试验将患者随机分为纳武利尤单抗±立体定向体部放疗（SBRT）组。采用1100和1630作为时间界限。根据首次输注或大部分SBRT的时间进行分类（例如，下午SBRT定义为1630之后进行两到三次放疗）。 结果 在62例患者中，上午使用纳武利尤单抗（n = 7，中位无进展生存期为175天）、下午使用纳武利尤单抗（n = 21，中位无进展生存期为58天）或中午使用纳武利尤单抗（n = 34，中位无进展生存期为67天；p = 0.8），中位无进展生存期无显著差异。上午进行SBRT（n = 4，中位无进展生存期为78天）、下午进行SBRT（n = 13，中位无进展生存期为111天）或中午进行SBRT（n = 15，中位无进展生存期为63天；p = 0.8），中位无进展生存期也无显著差异。3 - 4级毒性或客观缓解率（ORR）无显著差异。采用其他时间点的敏感性分析结果为阴性。 结论 进一步的研究可能会阐明昼夜节律对特定患者、肿瘤和治疗的影响；然而，我们在本研究中未发现显著影响。