First-Line Tislelizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Extensive-Stage SCLC: A Long-Term Survival and Programmed Death-Ligand 1 Subgroup Analysis From the Randomized, Phase 3 RATIONALE-312 Trial.

We report long-term follow-up (data cutoff: December 29, 2023) data.

我们报告了长期随访（数据截止日期：2023年12月29日）的数据。

Methods

Adults with previously untreated ES-SCLC were randomized 1:1 to four induction cycles of intravenous tislelizumab 200 mg or placebo once every 3 weeks plus investigator's choice of chemotherapy (intravenous carboplatin or cisplatin plus etoposide), followed by tislelizumab or placebo maintenance.

先前未接受治疗的广泛期小细胞肺癌（ES-SCLC）成人患者按1:1的比例随机接受四种静脉注射替雷利珠单抗200 mg或安慰剂，每3周一次，加上研究者选择的化疗方案（静脉注射卡铂或顺铂加依托泊苷），随后进行替雷利珠单抗或安慰剂维持治疗。

The primary end point was OS.

主要终点是总生存（OS）。

Results

With a median survival follow-up of 39.8 and 36.4 months in the tislelizumab (n = 227) and placebo (n = 230) arms, respectively, OS benefit in the intent-to-treat population was sustained compared with final analysis (median OS: 15.5 versus 13.5 mo, respectively; HR = 0.78; 95% CI: 0.63-0.95).

在替雷利珠单抗(n = 227)和安慰剂(n = 230)组中，中位生存随访时间分别为39.8个月和36.4个月。与最终分析相比，意向治疗人群的总生存获益持续存在（中位总生存期分别为15.5个月和13.5个月；风险比HR = 0.78；95%置信区间：0.63-0.95）。

Exploratory analyses found a consistent OS improvement favoring tislelizumab over placebo across programmed death-ligand 1 expression subgroups.

探索性分析发现，在程序性死亡配体-1表达亚组中，替雷利珠单抗相对于安慰剂的总生存改善是一致的。

The most frequently reported treatment-related adverse events in the tislelizumab and placebo arms were alopecia (78.4% versus 79.5%), anemia (76.7% versus 78.6%), and neutropenia (68.7% versus 70.3%).

在替雷利珠单抗和安慰剂组中，最常报告的治疗相关不良事件是脱发（78.4%对比79.5%）、贫血（76.7%对比78.6%）和中性粒细胞减少症（68.7%对比70.3%）。

Conclusions

Long-term follow-up data from RATIONALE-312 reported that patients with ES-SCLC treated with first-line tislelizumab plus chemotherapy had clinically meaningful and sustained improvements in OS compared with placebo plus chemotherapy in the intent-to-treat and programmed death-ligand 1-assessable populations.

RATIONALE-312的长期随访数据显示，与安慰剂加化疗相比，接受替雷利珠单抗联合化疗的一线治疗广泛期小细胞肺癌（ES-SCLC）患者的总生存期（OS）有临床意义且持续改善，这一结果在意向治疗人群和程序性死亡配体1可评估人群中均得到体现。

Tislelizumab plus chemotherapy was tolerable, with no new safety signals identified.

替雷利珠单抗联合化疗是可耐受的，未发现新的安全信号。

clinical_trial_information

ClinicalTrials.gov Identifier: NCT04005716.

ClinicalTrials.gov 注册号：NCT04005716。