免疫检查点抑制 (ICI) 是复发性或转移性头颈鳞状细胞癌 (R/M HNSCC) 的一线治疗方法，但围绕最佳治疗持续时间、ICI 再次挑战的益处和风险以及第一线与后续线的疗效仍存在疑问为了估计接受基于 ICI 的 R/M HNSCC 治疗的美国患者的生存率，比较治疗中断与继续治疗 1 或 2 年的结果，并评估免疫治疗重新挑战后的结果。这项回顾性、基于人群的队列研究包括Flatiron Health 全国肿瘤学数据库中 2015 年至 2023 年接受免疫疗法治疗 R/M HNSCC 的成年患者。数据截止日期为 2023 年 8 月 31 日；数据分析于2023年12月至2024年2月进行。1年和2年继续治疗与停止治疗；在停止 ICI 治疗至少 60 天后，不干预全身治疗（立即再挑战）或干预全身治疗（延迟再挑战）后再次进行 ICI 治疗。使用 Kaplan-Meier 方法分析 ICI 开始后的总生存期 (OS)。 Cox 多变量回归用于检查关键变量（治疗方案、人乳头瘤病毒 [HPV] 状态、东部肿瘤合作组 [ECOG] 表现状态）与生存率的关联。 该队列包括 4549 名接受 ICI 治疗的 R/M HNSCC 患者。包含疗法（中位 [IQR] 年龄，66 [59-72] 岁；3551 [78.1%] 男性；56 [1.2%] 亚洲人，260 [5.7%] 黑人或非裔美国人，3020 [66.4%] 白人，1213 [ 26.7%] 其他或未知种族；3226 [70.9%] ECOG 表现状态 0 或 1)。一线接受ICI的患者为3000例（65.9%），二线接受ICI的患者为1207例（26.5%）； 3478 名患者（76.5%）接受了 ICI 单药治疗。中位 (IQR) OS 为 10.9 (4.1-29.1) 个月，在一线治疗中接受 ICI 的患者更长（12.2 [4.8-32.0] vs 8.7 [3.2-22.4] 个月），患有 HPV 阳性癌症（16.6 [6.5] 个月） -43.9] vs 8.8 [3.5-24.0] 个月），ECOG 表现状态为 0 或 1（13.5 [5.2-33.9] vs 5.5 [2.0-13.7] 个月）。经调整分析，停止 ICI 的患者与继续 ICI 的患者在 1 年或 2 年之间没有生存差异。立即再挑战组中 ICI 再次挑战后的​​中位 (IQR) OS 为 15.7 (13.7-21.9) 个月，延迟再挑战组中为 9.9 (3.7-18.1) 个月。 在这项针对接受 ICI 的 R/M HNSCC 患者的大型队列研究中，基于治疗的生存估计密切反映了前线和后期环境中的临床试验结果。对于长期缓解者，在 1 或 2 年后停止 ICI 可能是一个合理的策略，不会影响生存。 ICI 再挑战与一部分患者的临床获益相关。

Immune checkpoint inhibition (ICI) is a frontline treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), but questions remain surrounding optimal duration of therapy, benefits and risks of ICI rechallenge, and efficacy in first vs subsequent lines of therapy.To estimate survival in US patients receiving ICI-based treatment for R/M HNSCC, compare outcomes associated with treatment discontinuation vs continuation at 1 or 2 years, and assess outcomes after immunotherapy rechallenge.This retrospective, population-based cohort study included adult patients in the Flatiron Health nationwide oncology database treated with immunotherapy for R/M HNSCC from 2015 to 2023. Data cutoff was August 31, 2023; data analysis was conducted from December 2023 to February 2024.Treatment continuation vs discontinuation at 1 and 2 years; rechallenge with ICI after at least a 60-day period off ICI therapy without intervening systemic treatment (immediate rechallenge), or with intervening systemic treatment (delayed rechallenge).Overall survival (OS) from ICI initiation was analyzed using the Kaplan-Meier method. Cox multivariable regression was used to examine associations of key variables (line of therapy, human papillomavirus [HPV] status, Eastern Cooperative Oncology Group [ECOG] performance status) with survival.The cohort included 4549 patients with R/M HNSCC who received ICI-containing therapy (median [IQR] age, 66 [59-72] years; 3551 [78.1%] male; 56 [1.2%] Asian, 260 [5.7%] Black or African American, 3020 [66.4%] White, 1213 [26.7%] other or unknown race; 3226 [70.9%] ECOG performance status 0 or 1). There were 3000 patients (65.9%) who received ICI in frontline and 1207 (26.5%) in second line; 3478 patients (76.5%) received ICI monotherapy. Median (IQR) OS was 10.9 (4.1-29.1) months and was longer in patients who received ICI in frontline therapy (12.2 [4.8-32.0] vs 8.7 [3.2-22.4] months), had HPV-positive cancer (16.6 [6.5-43.9] vs 8.8 [3.5-24.0] months), and had ECOG performance status 0 or 1 (13.5 [5.2-33.9] vs 5.5 [2.0-13.7] months). There were no survival differences on adjusted analysis between patients who stopped vs those who continued ICI at 1 or 2 years. Median (IQR) OS after ICI rechallenge was 15.7 (13.7-21.9) months in the immediate rechallenge group and 9.9 (3.7-18.1) months in the delayed rechallenge group.In this large cohort study of patients with R/M HNSCC receiving ICI-based therapy, survival estimates closely mirrored clinical trial results, both in frontline and later-line settings. Discontinuation of ICI in long-term responders at 1 or 2 years may be a reasonable strategy that does not appear to compromise survival. ICI rechallenge was associated with clinical benefit in a subset of patients.