Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133)
- CORRESPONDING AUTHOR：Stephen V. Liu, MD, Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road NW, Washington, DC20007; Twitter: @StephenVLiu; e-mail: Stephen.V.Liu@gunet.georgetown.edu
- Liu SV, Reck M, Mansfield AS, et al. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol 2021:Jco2001055.
PURPOSE 目的
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.
IMpower133（ClinicalTrials.gov标识符：NCT02763579）是一项随机，双盲I / III期研究，证明将阿特珠单抗（抗编程死亡配体1 [PD-L1]）添加到卡铂加依托泊苷（CP / ET）中与安慰剂加CP / ET相比，广泛期小细胞肺癌（ES-SCLC）的一线治疗显着改善了总生存期（OS）和无进展生存期（PFS）。并报道了最新的OS，疾病进展模式，安全性，探索性生物标志物（PD-L1，基于血液的肿瘤突变负担[bTMB]）。
PATIENTS AND METHODS 患者和方法
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.
未经治疗的广泛期SCLC患者被随机分配为1：1接受四个21天周期的卡铂（曲线下面积5 mg / mL / min [IV]，第1天）加上ET（100 mg / m2 IV，天） 1-3）与阿特珠单抗（1,200 mg IV，第1天）或安慰剂，然后维持atezolizumab或安慰剂，直到出现不可接受的毒性，疾病进展或失去临床益处为止。收集肿瘤标本，而且PD-L1试验不需要招募。在中期分析中，研究者评估的PFS和OS这两个主要终点在统计学上显着。并进行了更新的OS和PFS以及探索性生物标志物分析。
RESULTS 结果
Patients received atezolizumab plus CP/ET (n5201) or placebo plus CP/ET (n5202). 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 5 .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.
患者接受阿特珠单抗加CP / ET（n5201）或安慰剂加CP / ET（n5202）。在最新的分析中，OS的中位随访时间为22.9个月。发生了302人死亡。阿特珠单抗加CP / ET和安慰剂加CP / ET的中位OS分别为12.3和10.3个月（危险比，0.76；95％CI，0.60至0.95；描述性P=.0154）。在18个月时，阿特珠单抗加CP / ET和安慰剂加CP / ET组的存活率分别为34.0％和21.0％。无论PD-L1免疫组织化学或bTMB状况如何，患者都可从添加阿特珠单抗中获益。
CONCLUSION 结论
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.
在CP / ET将阿特珠单抗作为ES-SCLC的一线治疗剂，在更新后的分析中继续证实了改善的OS和可耐受的安全性，从而确认该方案是新的治疗标准。探索性分析表明，治疗益处与生物标志物状态无关。