From the Yale School of Medicine, New Haven, CT (R.S.H.); Weill Cornell Medical Center, New York (G.G.); the European Institute of Oncology, IRCCS, Milan (F.M.); Asklepios Lung Clinic, Munich-Gauting, Germany (N.R.); University Hospital Limoges, Limoges, France (A.V.); Centro de Pesquisa Clínica, Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil (C.H.B.); Nagoya University Graduate School of Medicine, Aichi, Japan (M. Morise); Vall d'Hebron University Hospital, Barcelona (E.F.); Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia (Z.A.); Prince of Songkla University-Hat Yai, Songkhla, Thailand (S.G.); Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, Istanbul, Turkey (M.O.); Genentech, South San Francisco, CA (W.Z., A.S., I.E., K.K., Y.D., H.K., X.W., M. McCleland, S.M.); the Medical University of Gdańsk, Gdansk, Poland (J.J.); and the Sarah Cannon Research Institute at Tennessee Oncology, Nashville (D.R.S.).
N Engl J Med. 2020 Oct 1;383(14):1328-1339. doi: 10.1056/NEJMoa1917346.
BACKGROUND: The efficacy and safety of the anti-programmed death ligand 1 (PD-L1) monoclonal antibody atezolizumab, as compared with those of platinum-based chemotherapy, as first-line treatment for patients with metastatic non-small-cell lung cancer (NSCLC) with PD-L1 expression are not known. METHODS: We conducted a randomized, open-label, phase 3 trial involving patients with metastatic nonsquamous or squamous NSCLC who had not previously received chemotherapy and who had PD-L1 expression on at least 1% of tumor cells or at least 1% of tumor-infiltrating immune cells as assessed by the SP142 immunohistochemical assay. Patients were assigned in a 1:1 ratio to receive atezolizumab or chemotherapy. Overall survival (primary end point) was tested hierarchically according to PD-L1 expression status among patients in the intention-to-treat population whose tumors were wild-type with respect to mutations or translocations. Within the population with and wild-type tumors, overall survival and progression-free survival were also prospectively assessed in subgroups defined according to findings on two PD-L1 assays as well as by blood-based tumor mutational burden. RESULTS: Overall, 572 patients were enrolled. In the subgroup of patients with and wild-type tumors who had the highest expression of PD-L1 (205 patients), the median overall survival was longer by 7.1 months in the atezolizumab group than in the chemotherapy group (20.2 months vs. 13.1 months; hazard ratio for death, 0.59; P = 0.01). Among all the patients who could be evaluated for safety, adverse events occurred in 90.2% of the patients in the atezolizumab group and in 94.7% of those in the chemotherapy group; grade 3 or 4 adverse events occurred in 30.1% and 52.5% of the patients in the respective groups. Overall and progression-free survival favored atezolizumab in the subgroups with a high blood-based tumor mutational burden. CONCLUSIONS: Atezolizumab treatment resulted in significantly longer overall survival than platinum-based chemotherapy among patients with NSCLC with high PD-L1 expression, regardless of histologic type. (Funded by F. Hoffmann-La Roche/Genentech; IMpower110 ClinicalTrials.gov number, NCT02409342.).
背景：抗程序性死亡配体 1（PD-L1）单克隆抗体阿特珠单抗与铂类化疗相比，作为 PD-L1 表达的转移性非小细胞肺癌（NSCLC）患者的一线治疗药物的疗效和安全性尚不清楚。
方法：我们进行了一项随机、开放标签、III 期临床试验，纳入了未经化疗且肿瘤细胞 PD-L1 表达至少为 1%或肿瘤浸润免疫细胞 PD-L1 表达至少为 1%的转移性非鳞状或鳞状 NSCLC 患者，这些患者通过 SP142 免疫组化检测评估。患者按照 1:1 的比例随机分配接受阿特珠单抗或化疗。总体生存（主要终点）根据意向治疗人群中肿瘤为野生型 突变或 易位患者的 PD-L1 表达状态进行分层检验。在 野生型肿瘤患者亚组中，还前瞻性评估了根据两种 PD-L1 检测以及基于血液的肿瘤突变负担结果定义的亚组中总生存期和无进展生存期。
结果：共有 572 名患者入组。在 野生型肿瘤患者亚组中，PD-L1 表达最高（205 例）的患者中，阿特珠单抗组的中位总生存期较化疗组延长 7.1 个月（20.2 个月 vs. 13.1 个月；死亡风险比，0.59；P=0.01）。在所有可评估安全性的患者中，阿特珠单抗组 90.2%的患者和化疗组 94.7%的患者发生不良反应；两组分别有 30.1%和 52.5%的患者发生 3 级或 4 级不良反应。在高血液肿瘤突变负担亚组中，阿特珠单抗总体和无进展生存期均优于化疗。
结论：在 PD-L1 高表达的 NSCLC 患者中，阿特珠单抗治疗的总生存期明显长于基于铂类的化疗，无论组织学类型如何。（由 F. Hoffmann-La Roche/Genentech 资助；IMpower110 临床试验.gov 编号，NCT02409342）。
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