Toripalimab Plus Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Lung Cancer: The Phase 3 EXTENTORCH Randomized Clinical Trial.

Background

To evaluate the efficacy and safety of toripalimab plus etoposide and platinum-based chemotherapy (EP) vs placebo plus EP as a first-line treatment for patients with ES-SCLC.

评估toripalimab联合依托泊苷和基于铂的化疗（EP）与安慰剂联合EP作为广泛期小细胞肺癌（ES-SCLC）患者一线治疗的有效性和安全性。

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, double-blind, placebo-controlledphase 3 randomized clinical trial (EXTENTORCH study) enrolled patients from September 26, 2019, to May 20, 2021, and was conducted at 49 sites in China.

设计、设置和参与者：这项多中心、双盲、安慰剂对照的III期随机临床试验（EXTENTORCH研究）从2019年9月26日开始，至2021年5月20日结束，在中国的49个地点进行。

Eligible patients had histologically or cytologically confirmed ES-SCLC without previous systemic antitumor therapy for ES-SCLC.

符合条件的患者具有组织学或细胞学证实的ES-SCLC，且之前未接受过针对ES-SCLC的全身性抗肿瘤治疗。

Data were analyzed between May 6, 2023, and June 1, 2024.

数据分析时间为2023年5月6日至2024年6月1日。

Methods

Patients were randomized (1:1) to receive toripalimab, 240 mg, or placebo plus EP every 3 weeks for up to 4 to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxic effects, or up to 2 years of treatment.

患者按1:1的比例随机接受toripalimab 240 mg或安慰剂加EP治疗，每3周一次，最多进行4至6个周期，之后继续使用toripalimab或安慰剂维持治疗，直至疾病进展、出现无法耐受的毒性反应或治疗满2年。

main_outcomes_and_measures

The primary end points were investigator-assessed progression-free survival(PFS) and overall survival(OS).

主要终点是研究者评估的无进展生存期（PFS）和总生存期（OS）。

Whole-exome sequencing results identified correlative biomarkers for clinical efficacy.

全外显子组测序结果确定了临床疗效的相关生物标志物。

Results

Among 595 screened patients, 442 eligible patients were randomized (median [range] age, 63 [30-77] years; 366 [82.8%] male); 223 patients were randomized to toripalimab plus EP, and 219 to placebo plus EP.

在595名筛查的患者中，442名符合条件的患者被随机分配（中位数[范围]年龄，63[30-77]岁；366名[82.8%]为男性）；223名患者被随机分配到托瑞利单抗加EP组，219名被随机分配到安慰剂加EP组。

By April 20, 2023, the median (range) survival follow-up was 13.7 (0.0-42.7) months.

截至2023年4月20日，中位（范围）生存随访时间为13.7（0.0-42.7）个月。

Compared with placebo, toripalimab improved investigator-assessed PFS (hazard ratio[HR], 0.67 [95% CI, 0.54-0.82]; P < .001), and significantly reduced the risk of death (HR, 0.80 [95% CI, 0.65-0.98]; P = .03).

与安慰剂相比，托瑞利珠单抗改善了研究者评估的无进展生存期（风险比[HR]，0.67 [95%置信区间，0.54-0.82]；P < .001），并且显著降低了死亡风险（HR，0.80 [95%置信区间，0.65-0.98]；P = .03）。

The median OS was 14.6 (95% CI, 12.9-16.6) months in the toripalimab group vs 13.3 (95% CI, 11.8-14.4) months in the placebo group.

托瑞利珠单抗组的中位总生存期为14.6（95%置信区间，12.9-16.6）个月，而安慰剂组为13.3（95%置信区间，11.8-14.4）个月。

Whole-exome sequencing results from 300 patients identified low intratumor heterogeneity, HLA-A11+ HLA-B62- haplotype, wild-type KMT2D and COL4A4, or sequence variations in CTNNA2 or SCN4A correlated with favorable PFS and OS in the toripalimab group.

对300名患者的全外显子组测序结果显示，低肿瘤内异质性、HLA-A11+ HLA-B62-单倍型、野生型KMT2D和COL4A4，或CTNNA2或SCN4A的序列变异与toripalimab组良好的无进展生存期（PFS）和总生存（OS）相关。

No new safety signals were observed.

未观察到新的安全信号。

Grade 3 or higher treatment-emergent adverse eventincidencewas similar between the toripalimab and placebo safety set groups (199 of 222 patients [89.6%] vs 193 of 216 patients [89.4%], respectively).

在托瑞利珠单抗和安慰剂安全集组中，3级或更高级别的治疗后不良事件发生率相似（分别占222名患者中的199名[89.6%]与216名患者中的193名[89.4%]）。

conclusions_and_relevance

In this phase 3 randomized clinical trial, adding toripalimab to first-line chemotherapy demonstrated significant improvements in PFS and OS for patients with ES-SCLC.

在这项III期随机临床试验中，将托瑞利珠单抗加入一线化疗显著改善了广泛期小细胞肺癌患者的无进展生存期（PFS）和总生存期（OS）。

The treatment exhibited an acceptable safety profile, supporting this combination regimen as a new treatment option for patients with ES-SCLC.

该治疗显示出可接受的安全性特征，支持将这种联合方案作为广泛期小细胞肺癌患者的新型治疗选择。

trial_registration

ClinicalTrials.gov Identifier: NCT04012606.

ClinicalTrials.gov 注册号：NCT04012606。