Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy. Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5% of TC or IC (TC2/3 or IC2/3 [TC or IC ≥ 5% PD-L1-expressing cells, respectively]) were enrolled. Atezolizumab 1,200 mg was administered intravenously every 3 weeks. Efficacy-evaluable patients (N = 659) comprised three cohorts: first line (cohort 1; n = 139); second line (cohort 2; n = 268); and third line or higher (cohort 3; n = 252). The primary end point was independent review facility-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Secondary end points included median duration of response, progression-free survival, and overall survival (OS). Results BIRCH met its primary objective of demonstrating a significant ORR versus historical controls. With a minimum of 12 months of follow-up, the independent review facility-assessed ORR was 18% to 22% for the three cohorts, and 26% to 31% for the TC3 or IC3 subgroup; most responses are ongoing. Responses occurred regardless of EGFR or KRAS mutation status. The median OS from an updated survival analysis (minimum of 20 month follow up) for cohort 1 was 23.5 months (26.9 months for TC3 or IC3 patients); the median OS in cohorts 2 and 3 was 15.5 and 13.2 months, respectively. The safety profile was similar across cohorts and consistent with previous atezolizumab monotherapy trials. Conclusion BIRCH demonstrated responses with atezolizumab monotherapy in patients with PD-L1-selected advanced NSCLC, with good tolerability. PD-L1 status may serve as a predictive biomarker for identifying patients most likely to benefit from atezolizumab.

中文翻译：

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Atezolizumab 作为程序性死亡配体 1 选定晚期非小细胞肺癌 (BIRCH) 患者的一线或后续治疗的 II 期试验

目的 BIRCH 旨在检查 atezolizumab，一种人源化抗程序性死亡配体 1 (PD-L1) 单克隆抗体，在晚期非小细胞肺癌 (NSCLC) 中跨治疗线的疗效。根据肿瘤细胞（TC）或肿瘤浸润免疫细胞（IC）上的 PD-L1 表达选择患者。患者和方法 符合条件的患者为晚期 NSCLC，无中枢神经系统转移，且之前接受过零至两线或多线化疗。使用 SP142 免疫组织化学测定在≥ 5% 的 TC 或 IC（TC2/3 或 IC2/3 [分别为 TC 或 IC ≥ 5% PD-L1 表达细胞]）表达 PD-L1 的患者被纳入研究。每 3 周静脉注射一次 Atezolizumab 1,200 mg。可评估疗效的患者 (N = 659) 包括三个队列：一线（队列 1；n = 139）；第二行（队列 2；n = 268）；和第三行或更高（队列 3；n = 252）。主要终点是独立审查机构评估的客观反应率（ORR；实体瘤反应评估标准 [RECIST] 1.1 版）。次要终点包括中位反应持续时间、无进展生存期和总生存期（OS）。结果 BIRCH 实现了其主要目标，即证明与历史对照相比显着的 ORR。在至少 12 个月的随访中，独立审查机构评估的三个队列的 ORR 为 18% 至 22%，TC3 或 IC3 亚组的 ORR 为 26% 至 31%；大多数反应都在进行中。无论 EGFR 或 KRAS 突变状态如何，都会发生反应。队列 1 的更新生存分析（最少 20 个月随访）的中位 OS 为 23.5 个月（TC3 或 IC3 患者为 26.9 个月）；队列 2 和队列 3 的中位 OS 分别为 15.5 和 13.2 个月。各队列的安全性特征相似，并且与之前的 atezolizumab 单药治疗试验一致。结论 BIRCH 在 PD-L1 选择的晚期 NSCLC 患者中证明了 atezolizumab 单药治疗的反应，具有良好的耐受性。PD-L1 状态可作为预测性生物标志物，用于识别最有可能从 atezolizumab 中获益的患者。