Shanghai Chest Hospital, Department of Oncology, Shanghai, People's Republic of China.
Cancer Hospital Chinese Academy of Medical Sciences, Beijing, Department of Medical Oncology, People's Republic of China.
J Thorac Oncol. 2021 Sep;16(9):1512-1522. doi: 10.1016/j.jtho.2021.05.005. Epub 2021 May 23.
Tislelizumab, an anti-programmed cell death protein-1 antibody, was specifically engineered to minimize FcɣR macrophage binding to abrogate antibody-dependent phagocytosis. Compared with chemotherapy alone, tislelizumab plus chemotherapy may improve clinical outcomes in patients with advanced nonsquamous NSCLC (nsq-NSCLC).
In this open-label phase 3 trial (RATIONALE 304; NCT03663205), patients with histologically confirmed stage IIIB or IV nsq-NSCLC were randomized (2:1) to receive either arm A: tislelizumab plus platinum (carboplatin or cisplatin) and pemetrexed every 3 weeks (Q3Ws) or arm B: platinum and pemetrexed alone Q3W during induction treatment, followed by intravenous maintenance pemetrexed Q3W. The primary end point was progression-free survival (PFS) assessed by an independent review committee; clinical response and safety and tolerability were secondary end points.
Overall, 332 patients (n = 222 [A]; n = 110 [B]) received treatment. With a median study follow-up of 9.8 months, PFS was significantly longer with tislelizumab plus chemotherapy compared with chemotherapy alone (median PFS: 9.7 versus 7.6 mo; hazard ratio = 0.645 [95% confidence interval: 0.462-0.902], p = 0.0044). In addition, response rates were higher and response duration was longer with combination therapy versus chemotherapy alone. Hematologic adverse events (AEs) were common in both treatment arms; the most reported AEs were grades 1 to 2 in severity. The most common grade greater than or equal to 3 AEs were associated with chemotherapy and included neutropenia (44.6% [A]; 35.5% [B]) and leukopenia (21.6% [A]; 14.5% [B]).
Addition of tislelizumab to chemotherapy resulted in significantly prolonged PFS, higher response rates, and longer response duration compared with chemotherapy alone, identifying a new potential option for first-line treatment of advanced nsq-NSCLC irrespective of disease stage.
替雷利珠单抗是一种抗程序性细胞死亡蛋白 1 抗体，专门设计用于最小化 FcγR 巨噬细胞结合以消除抗体依赖性吞噬作用。与单独化疗相比，替雷利珠单抗联合化疗可能改善晚期非鳞状 NSCLC（nsq-NSCLC）患者的临床结局。
在这项开放标签的 3 期试验（RATIONALE 304；NCT03663205）中，组织学证实为 IIIB 期或 IV 期非鳞状 NSCLC 的患者按 2:1 的比例随机分配至以下两组：A 组：替雷利珠单抗联合铂类（卡铂或顺铂）和培美曲塞每 3 周（Q3W）；B 组：单独使用铂类和培美曲塞 Q3W 进行诱导治疗，随后静脉维持培美曲塞 Q3W。主要终点是独立审查委员会评估的无进展生存期（PFS）；临床反应和安全性及耐受性为次要终点。
总体而言，332 名患者（n=222 [A]；n=110 [B]）接受了治疗。中位研究随访 9.8 个月时，与单独化疗相比，替雷利珠单抗联合化疗的 PFS 显著延长（中位 PFS：9.7 与 7.6 个月；风险比=0.645 [95%置信区间：0.462-0.902]，p=0.0044）。此外，联合治疗组的缓解率更高，缓解持续时间更长。两种治疗方案均常见血液学不良事件（AE）；报告最多的 AE 为 1-2 级严重程度。最常见的≥3 级 AE 与化疗相关，包括中性粒细胞减少症（44.6% [A]；35.5% [B]）和白细胞减少症（21.6% [A]；14.5% [B]）。
替雷利珠单抗联合化疗与单独化疗相比，可显著延长 PFS、提高缓解率并延长缓解持续时间，为晚期非鳞状 NSCLC 的一线治疗提供了新的潜在选择，无论疾病阶段如何。
