Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133).
Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133).
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DOI：
10.1200/jco.20.01055
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发表时间：
2021-02-20
期刊：
影响因子：
--
通讯作者：
Horn L
中科院分区：
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作者：
Liu SV;Reck M;Mansfield AS;Mok T;Scherpereel A;Reinmuth N;Garassino MC;De Castro Carpeno J;Califano R;Nishio M;Orlandi F;Alatorre-Alexander J;Leal T;Cheng Y;Lee JS;Lam S;McCleland M;Deng Y;Phan S;Horn L
IMpower133 （ClinicalTrials.gov identifier: NCT02763579）是一项随机、双盲、I/III期研究，该研究表明，将atezolizumab（抗程序性死亡配体1 [PD-L1]）加卡铂加依托泊苷（CP/ET）用于一线（1L）治疗广泛期小细胞肺癌（ES-SCLC），与安慰剂加CP/ET相比，总生存期（OS）和无进展生存期（PFS）显著改善。报告了最新的OS、疾病进展模式、安全性和探索性生物标志物（PD-L1、血液肿瘤突变负荷[bTMB]）。未经治疗的ES-SCLC患者被随机分配为1:1，接受4个21天周期的CP（曲线下面积5mg / mL/min静脉注射[IV]，第1天）加ET （100mg /m2 IV，第1-3天），atezolizumab （1200mg IV，第1天）或安慰剂，然后维持atezolizumab或安慰剂，直到不可接受的毒性，疾病进展或丧失临床益处。采集肿瘤标本；入组时不需要PD-L1检测。两个主要终点，研究者评估的PFS和OS，在中期分析中具有统计学意义。更新OS和PFS并进行探索性生物标志物分析。患者接受atezolizumab加CP/ET （n = 201）或安慰剂加CP/ET （n = 202）。在更新的分析中，OS的中位随访时间为22.9个月；已有302人死亡。atezolizumab加CP/ET组和安慰剂加CP/ET组的中位OS分别为12.3和10.3个月（风险比0.76;95% CI, 0.60 ~ 0.95；描述性P = 0.0154）。在18个月时，atezolizumab加CP/ET组和安慰剂加CP/ET组分别有34.0%和21.0%的患者存活。患者从添加atezolizumab中获益，无论PD-L1免疫组织化学或bTMB状态如何。在最新的分析中，将atezolizumab加入CP/ET作为ES-SCLC的1L治疗，继续显示出改善的OS和可耐受的安全性，证实该方案是一种新的治疗标准。探索性分析表明，治疗效果与生物标志物状态无关。
IMpower133 (ClinicalTrials.gov identifier: NCT02763579), a randomized, double-blind, phase I/III study, demonstrated that adding atezolizumab (anti-programmed death-ligand 1 [PD-L1]) to carboplatin plus etoposide (CP/ET) for first-line (1L) treatment of extensive-stage small-cell lung cancer (ES-SCLC) resulted in significant improvement in overall survival (OS) and progression-free survival (PFS) versus placebo plus CP/ET. Updated OS, disease progression patterns, safety, and exploratory biomarkers (PD-L1, blood-based tumor mutational burden [bTMB]) are reported. Patients with untreated ES-SCLC were randomly assigned 1:1 to receive four 21-day cycles of CP (area under the curve 5 mg per mL/min intravenously [IV], day 1) plus ET (100 mg/m2 IV, days 1-3) with atezolizumab (1,200 mg IV, day 1) or placebo, and then maintenance atezolizumab or placebo until unacceptable toxicity, disease progression, or loss of clinical benefit. Tumor specimens were collected; PD-L1 testing was not required for enrollment. The two primary end points, investigator-assessed PFS and OS, were statistically significant at the interim analysis. Updated OS and PFS and exploratory biomarker analyses were conducted. Patients received atezolizumab plus CP/ET (n = 201) or placebo plus CP/ET (n = 202). At the updated analysis, median follow-up for OS was 22.9 months; 302 deaths had occurred. Median OS was 12.3 and 10.3 months with atezolizumab plus CP/ET and placebo plus CP/ET, respectively (hazard ratio, 0.76; 95% CI, 0.60 to 0.95; descriptive P = .0154). At 18 months, 34.0% and 21.0% of patients were alive in atezolizumab plus CP/ET and placebo plus CP/ET arms, respectively. Patients derived benefit from the addition of atezolizumab, regardless of PD-L1 immunohistochemistry or bTMB status. Adding atezolizumab to CP/ET as 1L treatment for ES-SCLC continued to demonstrate improved OS and a tolerable safety profile at the updated analysis, confirming the regimen as a new standard of care. Exploratory analyses demonstrated treatment benefit independent of biomarker status.