Chu Tianqing, Zhang Wei, Zhang Bo, Zhong Runbo, Zhang Xueyan, Gu Aiqin, Shi Chunlei, Wang Huimin, Xiong Liwen, Lu Jun, Qian Jianlin, Zhang Yanwei, Dong Yu, Teng Jiajun, Gao Zhiqiang, Wang Weimin, Shen Yinchen, Nie Wei, Lim Jeong Uk, Mehta Hiren J, Neal Joel W, Lou Yuqing, Xu Jianlin, Zhong Hua, Han Baohui
Department of Respiratory, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
Division of Pulmonary, Critical Care and Allergy, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Transl Lung Cancer Res. 2022 Jul;11(7):1394-1404. doi: 10.21037/tlcr-22-438.
The evidence of combined therapies of multi-target agents in first-line treatment of advanced non-small cell lung cancer (NSCLC) was limited. This study aimed to evaluate the safety and efficacy of anlotinib combined with epidermal growth factor receptor () tyrosine kinase inhibitor (TKI), chemotherapy, or immune checkpoint inhibitor (ICI) in advanced NSCLC.
This open-label, three-arm, prospective study (NCT03628521) enrolled untreated locally advanced/metastatic NSCLC patients. Patients with mutation NSCLC received anlotinib and erlotinib (cohort A). Patients without // mutation received anlotinib combined with carboplatin plus pemetrexed/gemcitabine (cohort B), or sintilimab (cohort C). The primary outcomes were safety and objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), disease control rate (DCR), and overall survival (OS). Treatments were performed for at least 2 cycles and efficacy was evaluated every 2 cycles using RECIST version 1.1. Safety was assessed throughout the study.
A total of 30, 30, and 22 patients were enrolled in cohorts A, B, and C, respectively. There were 3 patients did not complete the treatment in cohort A. In cohorts A and B, ≥ grade 3 treatment-related adverse events (TRAEs) occurred in 77.3% and 60.0% of patients, respectively. The most common TRAEs were rash (10.0%) and decreased platelet count (30.0%) in cohorts A and B, respectively. The ORRs were 92.9% and 60.0% in cohorts A and B, respectively, and DCRs were 96.4% and 96.7%, respectively. The ORR and incidence of ≥ grade 3 TRAEs of cohort C were, which 72.7% and 54.5%, which had been published previously. Median PFSs [95% confidence interval (CI)] were 21.6 (15.6 to 24.9), 13.0 [10.5 to not estimated (NE)], and 15.6 (12.9 to NE) months in cohorts A, B, and C, respectively. Median OS was 28.1 (95% CI: 21.82 to NE) months in cohort B. The 24-month OS rates in cohorts A and C were 87.1% and 83.9%, respectively.
Anlotinib-based combinations with -TKI, chemotherapy, and ICI are well-tolerated and encouraging as first-line therapies for advanced NSCLC, which could be verified in future studies. Anlotinib-based combination might provide multiple choices for first-line treatment in patients with advanced NSCLC.
多靶点药物联合疗法用于晚期非小细胞肺癌（NSCLC）一线治疗的证据有限。本研究旨在评估安罗替尼联合表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）、化疗或免疫检查点抑制剂（ICI）治疗晚期NSCLC的安全性和疗效。
这项开放标签、三臂、前瞻性研究（NCT03628521）纳入未经治疗的局部晚期/转移性NSCLC患者。EGFR突变型NSCLC患者接受安罗替尼和厄洛替尼治疗（A组）。无EGFR/ALK/ROS1突变的患者接受安罗替尼联合卡铂加培美曲塞/吉西他滨治疗（B组），或信迪利单抗治疗（C组）。主要结局为安全性和客观缓解率（ORR）。次要终点包括无进展生存期（PFS）、疾病控制率（DCR）和总生存期（OS）。治疗至少进行2个周期，每2个周期使用RECIST 1.1版评估疗效。在整个研究过程中评估安全性。
A、B、C组分别纳入30、30和22例患者。A组有3例患者未完成治疗。A组和B组中，分别有77.3%和60.0%的患者发生≥3级治疗相关不良事件（TRAEs）。A组和B组最常见的TRAEs分别为皮疹（10.0%）和血小板计数降低（30.0%）。A组和B组的ORR分别为92.9%和60.0%，DCR分别为96.4%和96.7%。C组的ORR和≥3级TRAEs发生率分别为72.7%和54.5%，此前已发表。A、B、C组的中位PFS[95%置信区间（CI）]分别为21.6（15.6至24.9）、13.0[10.5至未估计（NE）]和15.6（12.9至NE）个月。B组的中位OS为28.1（95%CI：21.82至NE）个月。A组和C组的24个月OS率分别为87.1%和83.9%。
以安罗替尼为基础联合EGFR-TKI、化疗和ICI作为晚期NSCLC的一线治疗耐受性良好且效果令人鼓舞，这一点可在未来研究中得到验证。以安罗替尼为基础的联合方案可能为晚期NSCLC患者的一线治疗提供多种选择。
