Xu Manyi, Wang Yanhua, Wang Ke, Hao Yue, Xu Chunwei, Shi Lei, Song Zhengbo
Department of Clinical Trial, Zhejiang Cancer Hospital, No.1 East Banshan Road, Gongshu District, Hangzhou, Zhejiang, 310022, China.
Affiliated Hospital of Medical School, Nanjing University, Jinling Hospital, Nanjing, 210002, China.
Invest New Drugs. 2024 Dec;42(6):703-715. doi: 10.1007/s10637-024-01483-7. Epub 2024 Dec 2.
The efficacy of immune rechallenge in patients with advanced non-small cell lung cancer (NSCLC) who responded well to initial immune checkpoint inhibitor (ICI) treatment is becoming a research hotspot. This study was aimed at describing the survival and clinical characteristics after immune rechallenge in initial immunotherapy responders.
We retrospectively identified 104 patients with advanced NSCLC who responded well in the first ICI and were rechallenged with immunotherapy to treat progression between January 2018 and June 2023 at Zhejiang Cancer Hospital. Progression-free survival (PFS) 2 and overall survival (OS) were defined as the time from the first day of the second ICI to the date of progression, death, or last follow-up.
Of 104 enrolled patients, 33 received immune monotherapy, and 71 were rechallenged with combination therapy (34 combined with anti-angiogenesis therapy). Patients with an initial immunotherapy duration exceeding 12 months, compared with a duration within 12 months, achieved a significantly prolonged mPFS2 and mOS (PFS2: 9.2 vs. 3.4 months, P < 0.001; OS: 25.5 vs. 10.7 months, P = 0.006). Patients rechallenged with combination therapy had significantly longer PFS2 than those receiving monotherapy (5.8 vs. 2.5 months, P = 0.040), and showed a favorable OS trend (15.9 vs. 10.1 months, P = 0.301). A significant difference in PFS2, particularly for patients receiving combined treatment with anti-angiogenesis therapy (8.7 vs. 4.6 months, P = 0.011), and a tendency toward longer OS (25.3 vs. 13.7 months, P = 0.090), were observed. Multivariate analysis identified long-term treatment duration (P = 0.005) and combined treatment with anti-angiogenesis therapy (P = 0.030) as independent positive factors associated with PFS after rechallenge.
Immune rechallenge is recommend for responders with a prolonged initial immunotherapy duration. Combination therapy, particularly that including anti-angiogenic therapy, is an alternative effective approach to immune rechallenge.
对于初始免疫检查点抑制剂（ICI）治疗反应良好的晚期非小细胞肺癌（NSCLC）患者，免疫再挑战的疗效正成为一个研究热点。本研究旨在描述初始免疫治疗反应者免疫再挑战后的生存情况和临床特征。
我们回顾性纳入了2018年1月至2023年6月在浙江省肿瘤医院接受首次ICI治疗反应良好且因疾病进展接受免疫再挑战治疗的104例晚期NSCLC患者。无进展生存期（PFS）2和总生存期（OS）定义为从第二次ICI治疗的第一天到疾病进展、死亡或最后一次随访的时间。
104例入组患者中，33例接受免疫单药治疗，71例接受联合治疗再挑战（34例联合抗血管生成治疗）。初始免疫治疗持续时间超过12个月的患者与持续时间在12个月以内的患者相比，mPFS2和mOS显著延长（PFS2：9.2个月对3.4个月，P<0.001；OS：25.5个月对10.7个月，P=0.006）。接受联合治疗再挑战的患者PFS2显著长于接受单药治疗的患者（5.8个月对2.5个月，P=0.040），且OS有良好趋势（15.9个月对Io.1个月，P=0.301）。观察到PFS2有显著差异，特别是对于接受抗血管生成治疗联合治疗的患者（8.7个月对4.6个月，P=0.011），且OS有延长趋势（25.3个月对13.7个月，P=0.090）。多因素分析确定长期治疗持续时间（P=0.005）和抗血管生成治疗联合治疗（P=0.030）是再挑战后与PFS相关的独立阳性因素。
对于初始免疫治疗持续时间延长的反应者，推荐进行免疫再挑战。联合治疗，特别是包括抗血管生成治疗的联合治疗，是免疫再挑战的一种有效替代方法。
