Harvard Medical School, Boston, Massachussetts, USA.
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
J Immunother Cancer. 2024 Jul 25;12(7):e009495. doi: 10.1136/jitc-2024-009495.
Immunotherapy can be associated with prolonged disease control even after cessation of treatment without the need for further cancer-directed therapy. Treatment-related adverse events (TRAEs) can also persist after discontinuation of therapy. Treatment-free survival (TFS) with and without toxicity as a component of a partitioned survival model can characterize patient survival time, which is not captured by standard outcome measures.
Data from 1096 patients with advanced renal cell carcinoma treated with first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in the CheckMate 214 trial were analyzed. TFS was defined as the area between two Kaplan-Meier curves for time from randomization to protocol therapy discontinuation and time from randomization to subsequent systemic therapy initiation or death, estimated as the difference in 60-month restricted mean times with confidence intervals (CIs) obtained using bootstrap sampling. Time on protocol therapy and TFS were further characterized as time with and without grade 2+ and 3+TRAEs. Survival functions were estimated in subgroups including International Metastatic Renal Cell Carcinoma Database Consortium risk groups using the Kaplan-Meier method.
At 5 years from randomization, 48% of patients treated with NIVO+IPI and 37% of patients treated with SUN were alive. In the intent-to-treat population, 18% of the NIVO+IPI-treated and 5% of SUN-treated patients are surviving treatment-free. For favorable-risk patients, the 60-month mean TFS was 14.4 months for NIVO+IPI versus 5.5 months for SUN (difference 8.9 months (95% CI 4.9 to 12.8)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 5.0 and 2.1 months, respectively, and with grade 3+TRAEs was 1.2 and 0.3 months, respectively. For intermediate/poor-risk patients, the 60-month mean TFS was 10.1 months for NIVO+IPI versus 4.1 months for SUN (difference 6.1 months (95% CI 4.2 to 7.9)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 4.0 versus 2.0 months, respectively, and 0.6 versus 0.3 months with grade 3+TRAEs.
Although overall survival was similar, favorable-risk patients treated with NIVO+IPI spent more time surviving treatment-free with and without toxicity versus SUN after 60 months of follow-up. Intermediate/poor-risk patients treated with NIVO+IPI had longer survival and longer TFS without toxicity versus SUN.
NCT02231749.
免疫疗法可在停止治疗后延长疾病控制时间，即使在无需进一步癌症靶向治疗的情况下也是如此。治疗相关不良反应（TRAEs）也可能在治疗停止后持续存在。无毒性和有毒性的治疗无失败生存期（TFS）作为分割生存模型的一部分，可用于描述患者的生存时间，而这一指标无法通过标准的疗效评估来体现。
对 CheckMate 214 试验中 1096 例接受一线纳武单抗联合伊匹单抗（NIVO+IPI）与舒尼替尼（SUN）治疗的晚期肾细胞癌患者的数据进行了分析。TFS 定义为从随机分组到方案治疗停止和从随机分组到后续系统治疗开始或死亡的时间之间的两个 Kaplan-Meier 曲线之间的区域，使用 bootstrap 抽样获得的 60 个月限制平均时间的差异并通过置信区间（CI）进行估计。协议治疗期间的时间和 TFS 进一步以 2+级和 3+级 TRAEs 有无为特征进行描述。采用 Kaplan-Meier 法，在包括国际转移性肾细胞癌数据库联盟风险组在内的亚组中评估生存功能。
从随机分组起 5 年时，接受 NIVO+IPI 治疗的患者中有 48%和接受 SUN 治疗的患者中有 37%存活。在意向治疗人群中，NIVO+IPI 治疗组中有 18%和 SUN 治疗组中有 5%的患者正在接受无治疗的生存。对于低危患者，NIVO+IPI 的 60 个月平均 TFS 为 14.4 个月，而 SUN 的 60 个月平均 TFS 为 5.5 个月（差异为 8.9 个月（95%CI 4.9 至 12.8））。NIVO+IPI 与 SUN 治疗组中 2+级 TRAEs 的 TFS 分别为 5.0 个月和 2.1 个月，3+级 TRAEs 的 TFS 分别为 1.2 个月和 0.3 个月。对于中危/高危患者，NIVO+IPI 的 60 个月平均 TFS 为 10.1 个月，而 SUN 的 60 个月平均 TFS 为 4.1 个月（差异为 6.1 个月（95%CI 4.2 至 7.9））。NIVO+IPI 与 SUN 治疗组中 2+级 TRAEs 的 TFS 分别为 4.0 个月和 2.0 个月，3+级 TRAEs 的 TFS 分别为 0.6 个月和 0.3 个月。
尽管总生存情况相似，但接受 NIVO+IPI 治疗的低危患者在 60 个月的随访后，无毒性和有毒性的 TFS 时间均长于接受 SUN 治疗的患者。接受 NIVO+IPI 治疗的中危/高危患者无毒性的 TFS 时间长于接受 SUN 治疗的患者，总生存时间也长于接受 SUN 治疗的患者。
NCT02231749。
