阿特珠单抗对比多西他赛用于治疗晚期 NSCLC 患者：POPLAR 和 OAK 两项随机、2 期和 3 期临床试验的最终结果。
Atezolizumab Versus Docetaxel in Pretreated Patients With NSCLC: Final Results From the Randomized Phase 2 POPLAR and Phase 3 OAK Clinical Trials.
机构信息
Institut Universitaire du Cancer de Toulouse, Toulouse University Hospital, Université Paul Sabatier, Toulouse, France.
Department of Thoracic Oncology, Lungenfachklinik Immenhausen, Immenhausen, Germany.
出版信息
J Thorac Oncol. 2021 Jan;16(1):140-150. doi: 10.1016/j.jtho.2020.09.022. Epub 2020 Nov 6.
INTRODUCTION
The phase 2 POPLAR and phase 3 OAK studies of the anti-programmed death-ligand 1 (PD-L1) immunotherapy atezolizumab in patients with previously treated advanced NSCLC revealed significant improvements in survival versus docetaxel (p = 0.04 and 0.0003, respectively). Longer follow-up permits evaluation of continued benefit of atezolizumab. This study reports the final overall survival (OS) and safety findings from both trials.
METHODS
POPLAR randomized 287 patients (atezolizumab, 144; docetaxel, 143) and OAK randomized 1225 patients (atezolizumab, 613; docetaxel, 612). The patients received atezolizumab (1200 mg fixed dose) or docetaxel (75 mg/m) every 3 weeks. Efficacy and safety outcomes were evaluated.
RESULTS
A longer OS was observed in patients receiving atezolizumab versus docetaxel in POPLAR (median OS = 12.6 mo versus 9.7 mo; hazard ratio = 0.76, 95% confidence interval [CI]: 0.58-1.00) and OAK (median OS = 13.3 versus 9.8 mo; hazard ratio = 0.78, 95% CI: 0.68-0.89). The 4-year OS rates in POPLAR were 14.8% (8.7-20.8) and 8.1% (3.2-13.0) and those in OAK were 15.5% (12.4-18.7) and 8.7% (6.2-11.3) for atezolizumab and docetaxel, respectively. Atezolizumab had improved OS benefit compared with docetaxel across all PD-L1 expression and histology groups. Most 4-year survivors in the docetaxel arms received subsequent immunotherapy (POPLAR, 50%; OAK, 65%). Of the 4-year survivors, most had Eastern Cooperative Oncology Group performance status of 0 and nonsquamous histological classification and approximately half were responders (POPLAR: atezolizumab, seven of 15; docetaxel, three of four; OAK: atezolizumab, 24 of 43; docetaxel, 11 of 26). Treatment-related grade 3/4 adverse events occurred in 27% and 16% of atezolizumab 4-year survivors in POPLAR and OAK, respectively.
CONCLUSIONS
Long-term follow-up suggests a consistent survival benefit with atezolizumab versus docetaxel in patients with previously treated NSCLC regardless of PD-L1 expression, histology, or subsequent immunotherapy. Atezolizumab had no new safety signals, and the safety profile was similar to that in previous studies.
简介
抗程序性死亡配体 1（PD-L1）免疫疗法阿特珠单抗在先前治疗过的晚期 NSCLC 患者中的 2 期 POPLAR 和 3 期 OAK 研究显示，与多西他赛相比，生存有显著改善（分别为 p=0.04 和 0.0003）。更长时间的随访可评估阿特珠单抗的持续获益。本研究报告了两项试验的最终总生存（OS）和安全性结果。
方法
POPLAR 随机分配了 287 例患者（阿特珠单抗，144 例；多西他赛，143 例），OAK 随机分配了 1225 例患者（阿特珠单抗，613 例；多西他赛，612 例）。患者每 3 周接受一次 1200mg 固定剂量的阿特珠单抗或 75mg/m 的多西他赛。评估了疗效和安全性结局。
结果
在 POPLAR 和 OAK 中，接受阿特珠单抗治疗的患者比接受多西他赛治疗的患者观察到更长的 OS（中位 OS：12.6 个月 vs 9.7 个月；风险比=0.76，95%置信区间[CI]：0.58-1.00）。POPLAR 的 4 年 OS 率分别为 14.8%（8.7-20.8）和 8.1%（3.2-13.0），OAK 分别为 15.5%（12.4-18.7）和 8.7%（6.2-11.3）。在所有 PD-L1 表达和组织学组中，阿特珠单抗与多西他赛相比均具有改善 OS 的获益。多西他赛组中，大多数 4 年生存者接受了后续免疫治疗（POPLAR，50%；OAK，65%）。在 4 年生存者中，大多数患者的东部肿瘤协作组表现状态为 0，非鳞状组织学分类，大约一半是应答者（POPLAR：阿特珠单抗，15 例中有 7 例；多西他赛，4 例中有 3 例；OAK：阿特珠单抗，43 例中有 24 例；多西他赛，26 例中有 11 例）。POPLAR 和 OAK 中，分别有 27%和 16%的阿特珠单抗 4 年生存者发生了与治疗相关的 3/4 级不良事件。
结论
无论 PD-L1 表达、组织学或后续免疫治疗如何，在先前治疗过的 NSCLC 患者中，与多西他赛相比，长期随访提示阿特珠单抗具有一致的生存获益。阿特珠单抗无新的安全性信号，且安全性与之前的研究相似。
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