Zhang Shuang, Li Shuang, Cui Yanan, Zhao Peiyan, Sun Xiaodan, Cheng Ying
Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, China.
Big Data Center of Clinical, Jilin Cancer Hospital, Changchun, China.
Front Oncol. 2021 Jul 14;11:696010. doi: 10.3389/fonc.2021.696010. eCollection 2021.
The combination of immune checkpoint inhibitors (ICIs) and chemotherapy is known to improve overall survival (OS) in patients with extensive-stage small cell lung cancer (ES-SCLC). ICIs have different response patterns and survival kinetics characteristics from those of the traditional chemotherapy. In first-line treatment for ES-SCLC, there is an urgent need for surrogate endpoints for the early and accurate prediction of OS. This study aimed to assess progression-free survival (PFS), milestone OS rate, milestone restricted mean survival time (RMST), overall response rate (ORR), and disease control rate (DCR) as proposed surrogate endpoints for OS in ES-SCLC for first-line immunotherapy trials.
Between January 1, 2013, and December 2020, published articles on randomized clinical trials of ICIs plus chemotherapy in patients with ES-SCLC as first-line therapy were searched in PubMed. Abstracts from the ESMO, ASCO, and WCLC, reported from 2018 onwards, were also searched. A weighted regression analysis based on the weighted least squares method was performed on log-transformed estimates of treatment effect, and the determination coefficient (R) was calculated to evaluate the association between treatment effect on the surrogate endpoint and OS.
Seven trials, representing 3,009 patients, were included to make up a total of 16 analyzed arms. The ratio of the 12-month OS milestone rate (r = -0.790, P = 0.011, R = 0.717) and 12-month OS milestone RMST (r = 0.798, P = 0.010, R = 0.702) was strongly correlated with the hazard ratio (HR) for OS. The strongest association was observed between the ratio of the 24-month OS milestone RMST and the HR for OS (r = 0.922, P = 0.001, R = 0.825). No associations were observed between the HR for OS and PFS and the RR for ORR and DCR.
The results suggested a strong correlation among the ratio of OS milestone rates at 12 months, ratios of OS milestone RMSTs at 12 and 24 months, and HR for OS. The results indicate that OS milestone rates and OS milestone RMSTs could be considered surrogate endpoints of OS in future first-line immunotherapy trials for ES-SCLC.
免疫检查点抑制剂（ICI）与化疗联合使用可提高广泛期小细胞肺癌（ES-SCLC）患者的总生存期（OS）。ICI具有与传统化疗不同的反应模式和生存动力学特征。在ES-SCLC的一线治疗中，迫切需要能够早期准确预测OS的替代终点。本研究旨在评估无进展生存期（PFS）、里程碑式总生存率、里程碑式受限平均生存时间（RMST）、总缓解率（ORR）和疾病控制率（DCR），将其作为ES-SCLC一线免疫治疗试验中OS的替代终点。
在2013年1月1日至2020年12月期间，在PubMed上检索已发表的关于ICI联合化疗作为一线治疗ES-SCLC患者的随机临床试验文章。还检索了2018年起ESMO、ASCO和WCLC报道的摘要。对治疗效果的对数转换估计值进行基于加权最小二乘法的加权回归分析，并计算决定系数（R），以评估替代终点的治疗效果与OS之间的关联。
纳入7项试验，共3009例患者，组成16个分析组。12个月总生存率里程碑率（r = -0.790，P = 0.011，R = 0.717）和12个月总生存率里程碑RMST（r = 0.798，P = 0.010，R = 0.702）与总生存期风险比（HR）密切相关。在24个月总生存率里程碑RMST与总生存期HR之间观察到最强的关联（r = 0.922，P = 0.001，R = 0.825）。在总生存期HR与PFS以及ORR和DCR的RR之间未观察到关联。
结果表明12个月时总生存率里程碑率、12个月和24个月时总生存率里程碑RMST的比率与总生存期HR之间存在强相关性。结果表明，在未来ES-SCLC的一线免疫治疗试验中，总生存率里程碑率和总生存率里程碑RMST可被视为总生存期的替代终点。
