Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
JAMA Oncol. 2023 Aug 1;9(8):1075-1082. doi: 10.1001/jamaoncol.2023.1891.
For patients with advanced non-small cell lung cancer (NSCLC) treated with frontline immunotherapy-based treatment, the optimal duration of immune checkpoint inhibitor (ICI) treatment is unknown.
To assess practice patterns surrounding ICI treatment discontinuation at 2 years and to evaluate the association of duration of therapy with overall survival in patients who received fixed-duration ICI therapy for 2 years vs those who continued therapy beyond 2 years.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based cohort study included adult patients in a clinical database diagnosed with advanced NSCLC from 2016 to 2020, who received frontline immunotherapy-based treatment. The data cutoff was August 31, 2022; data analysis was conducted from October 2022 to January 2023.
Treatment discontinuation at 2 years (between 700 and 760 days, fixed duration) vs continued treatment beyond 2 years (greater than 760 days, indefinite duration).
Overall survival from 760 days was analyzed using Kaplan-Meier methods. Multivariable Cox regression that adjusted for patient-specific and cancer-specific factors was used to compare survival beyond 760 days between the fixed-duration group and the indefinite-duration group.
Of 1091 patients in the analytic cohort who were still on ICI treatment at 2 years after exclusion criteria for death and progression were applied, 113 patients (median [IQR] age, 69 [62-75] years; 62 [54.9%] female; 86 [76.1%] White) were in the fixed-duration group, and 593 patients (median [IQR] age, 69 [62-76] years; 282 [47.6%] female; 414 [69.8%] White) were in the indefinite-duration group. Patients in the fixed-duration group were more likely to have a history of smoking (99% vs 93%; P = .01) and be treated at an academic center (22% vs 11%; P = .001). Two-year overall survival from 760 days was 79% (95% CI, 66%-87%) in the fixed-duration group and 81% (95% CI, 77%-85%) in the indefinite-duration group. There was no statistically significant difference in overall survival between patients in the fixed-duration and indefinite-duration groups, either on univariate (hazard ratio [HR] 1.26; 95% CI, 0.77-2.08; P = .36) or multivariable (HR 1.33; 95% CI, 0.78-2.25; P = .29) Cox regression. Approximately 1 in 5 patients discontinued immunotherapy at 2 years in the absence of progression.
In a retrospective clinical cohort of patients with advanced NSCLC who were treated with immunotherapy and were progression-free at 2 years, approximately only 1 in 5 discontinued treatment. The lack of statistically significant overall survival advantage for the indefinite-duration cohort on adjusted analysis provides reassurance to patients and clinicians who wish to discontinue immunotherapy at 2 years.
对于接受一线免疫治疗的晚期非小细胞肺癌 (NSCLC) 患者，免疫检查点抑制剂 (ICI) 治疗的最佳持续时间尚不清楚。
评估在第 2 年时停止 ICI 治疗的实践模式，并评估在接受固定疗程 2 年的 ICI 治疗的患者与继续治疗超过 2 年的患者之间，治疗持续时间与总生存期的相关性。
设计、设置和参与者：这项回顾性、基于人群的队列研究纳入了 2016 年至 2020 年期间在临床数据库中诊断为晚期 NSCLC 的成年患者，他们接受了一线免疫治疗。数据截止日期为 2022 年 8 月 31 日；数据分析于 2022 年 10 月至 2023 年 1 月进行。
第 2 年（700 至 760 天，固定疗程）时停止治疗与继续治疗超过 2 年（大于 760 天，无限期疗程）。
从 760 天开始分析总生存期，使用 Kaplan-Meier 方法。使用调整了患者特异性和癌症特异性因素的多变量 Cox 回归，比较了固定疗程组和无限期疗程组在 760 天后的生存情况。
在排除死亡和进展的排除标准后，在分析队列中有 1091 名患者在第 2 年仍在接受 ICI 治疗，其中 113 名患者（中位[IQR]年龄，69 [62-75] 岁；62 [54.9%] 为女性；86 [76.1%] 为白人）处于固定疗程组，593 名患者（中位[IQR]年龄，69 [62-76] 岁；282 [47.6%] 为女性；414 [69.8%] 为白人）处于无限期疗程组。固定疗程组的患者更有可能有吸烟史（99%比 93%；P = .01）和在学术中心接受治疗（22%比 11%；P = .001）。固定疗程组从第 760 天开始的 2 年总生存期为 79%（95% CI，66%-87%），无限期疗程组为 81%（95% CI，77%-85%）。在单变量（风险比[HR] 1.26；95% CI，0.77-2.08；P = .36）或多变量（HR 1.33；95% CI，0.78-2.25；P = .29）Cox 回归中，固定疗程组和无限期疗程组的总生存期均无统计学显著差异。大约每 5 名患者中有 1 名在第 2 年时没有进展就停止了免疫治疗。在调整后的分析中，无限期疗程组的总生存期没有统计学显著优势，这为希望在第 2 年停止免疫治疗的患者和临床医生提供了保证。
