Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, P.R. China.
Department of Oncology, The First Affiliated Hospital Zhejiang University, Hangzhou, P.R. China.
Clin Cancer Res. 2021 Mar 1;27(5):1296-1304. doi: 10.1158/1078-0432.CCR-20-3136. Epub 2020 Dec 15.
Our preclinical work suggests that appropriate angiogenesis inhibition could potentiate PD-1/PD-L1 blockade via alleviating hypoxia, increasing infiltration of CD8 T cells and reducing recruitment of tumor-associated macrophages. We hereby conducted a clinical trial to evaluate this combination in pretreated patients with advanced non-small cell lung cancer (NSCLC).
The study included phase Ib apatinib dose-escalation and phase II expansion cohorts. Patients received apatinib at doses of 250-500 mg orally once daily, in combination with camrelizumab 200 mg intravenously every 2 weeks.
From March 2017 to October 2018, 105 chemotherapy-pretreated patients with nonsquamous NSCLC were enrolled and received apatinib 250 mg (recommended phase II dose) and camrelizumab. Among them, one (1.0%) complete response, 28 (26.7%) partial responses, and 48 (45.7%) stable diseases were observed. In the efficacy-evaluable population ( = 94), objective response rate (ORR) was 30.9% [95% confidence interval (CI), 21.7-41.2]. The median progression-free survival was 5.7 months (95% CI, 4.5-8.8) and overall survival was 15.5 months (95% CI, 10.9-24.5). Efficacy of combination therapy was evident across all PD-L1 and tumor mutation burden subgroups, and appeared to be improved in patients with STK11/KEAP1 mutation (mutant vs. wild-type, ORR: 42.9% vs. 28.1%; 1-year survival rate: 85.1% vs. 53.1%). No unexpected adverse events were observed.
Combined apatinib and camrelizumab showed encouraging antitumor activity and acceptable toxicity in chemotherapy-pretreated patients with advanced nonsquamous NSCLC. Patients with STK11/KEAP1 mutation might derive more benefits from this combination. We will validate these results in an ongoing phase III trial (NCT04203485).
我们的临床前研究表明，适当的血管生成抑制可能通过减轻缺氧、增加 CD8 T 细胞浸润和减少肿瘤相关巨噬细胞募集来增强 PD-1/PD-L1 阻断作用。因此，我们在此进行了一项临床试验，以评估该联合疗法在预处理的晚期非小细胞肺癌（NSCLC）患者中的疗效。
该研究包括 Ib 期阿帕替尼剂量递增和 II 期扩展队列。患者接受阿帕替尼 250-500mg 口服，每日一次，联合卡瑞利珠单抗 200mg 静脉输注，每 2 周一次。
从 2017 年 3 月至 2018 年 10 月，共纳入 105 例化疗预处理的非鳞状 NSCLC 患者，接受阿帕替尼 250mg（推荐的 II 期剂量）和卡瑞利珠单抗治疗。其中，1 例（1.0%）完全缓解，28 例（26.7%）部分缓解，48 例（45.7%）病情稳定。在可评估疗效的人群（n=94）中，客观缓解率（ORR）为 30.9%[95%置信区间（CI），21.7-41.2]。中位无进展生存期为 5.7 个月（95%CI，4.5-8.8），总生存期为 15.5 个月（95%CI，10.9-24.5）。联合治疗的疗效在所有 PD-L1 和肿瘤突变负荷亚组中均明显，在 STK11/KEAP1 突变患者中似乎有所改善（突变 vs. 野生型，ORR：42.9% vs. 28.1%；1 年生存率：85.1% vs. 53.1%）。未观察到意外的不良反应。
阿帕替尼联合卡瑞利珠单抗在化疗预处理的晚期非鳞状 NSCLC 患者中显示出令人鼓舞的抗肿瘤活性和可接受的毒性。STK11/KEAP1 突变患者可能从该联合治疗中获益更多。我们将在一项正在进行的 III 期试验（NCT04203485）中验证这些结果。
