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: [email protected] 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識別符號：NCT02763579）是一項隨機，雙盲I / III期研究，證明將阿特珠單抗（抗程式設計死亡配體1 [PD-L1]）新增到卡鉑加依託泊苷（CP / ET）中與安慰劑加CP / ET相比，廣泛期小細胞肺癌（ES-SCLC）的一線治療顯著改善了總生存期（OS）和無進展生存期（PFS）。並報道了最新的OS，疾病進展模式，安全性，探索性生物標誌物（PD-L1，基於血液的腫瘤突變負擔[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.
未經治療的廣泛期SCLC患者被隨機分配為1：1接受四個21天週期的卡鉑（曲線下面積5 mg / mL / min [IV]，第1天）加上ET（100 mg / m2 IV，天） 1-3）與阿特珠單抗（1,200 mg IV，第1天）或安慰劑，然後維持atezolizumab或安慰劑，直到出現不可接受的毒性，疾病進展或失去臨床益處為止。收集腫瘤標本，而且PD-L1試驗不需要招募。在中期分析中，研究者評估的PFS和OS這兩個主要終點在統計學上顯著。並進行了更新的OS和PFS以及探索性生物標誌物分析。
RESULTS 結果
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.
患者接受阿特珠單抗加CP / ET（n5201）或安慰劑加CP / ET（n5202）。在最新的分析中，OS的中位隨訪時間為22.9個月。發生了302人死亡。阿特珠單抗加CP / ET和安慰劑加CP / ET的中位OS分別為12.3和10.3個月（危險比，0.76；95％CI，0.60至0.95；描述性P=.0154）。在18個月時，阿特珠單抗加CP / ET和安慰劑加CP / ET組的存活率分別為34.0％和21.0％。無論PD-L1免疫組織化學或bTMB狀況如何，患者都可從新增阿特珠單抗中獲益。
CONCLUSION 結論
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將阿特珠單抗作為ES-SCLC的一線治療劑，在更新後的分析中繼續證實了改善的OS和可耐受的安全性，從而確認該方案是新的治療標準。探索性分析表明，治療益處與生物標誌物狀態無關。