Wu Jun-Wei, Zhou Chen-Fei, Han Zheng-Xiang, Zhang Huan, Yan Jun, Chen Jun, Wang Chun-Bin, Qin Zhi-Quan, Mao Yong, Tang Xin-Yu, Zhu Liang-Jun, Wei Xiao-Wei, Cui Dong-Hai, Yang Xiu-Li, Shi Min, Zhao Li-Qin, Jiang Jin-Ling, Zhu Wei-You, Wang Hong-Mei, Wang Chun, Zhu Ling-Jun, Zhang Jun
Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Signal Transduct Target Ther. 2024 Dec 9;9(1):344. doi: 10.1038/s41392-024-02051-4.
This multicohort phase II trial (ALTER-G-001; NCT05262335) aimed to assess the efficacy of first-line anlotinib plus chemotherapy for gastrointestinal (GI) cancer patients with unresectable liver metastases. Eligible patients with colorectal cancer (Cohort A) or noncolorectal and nonesophageal GI cancer (Cohort C) received six cycles of anlotinib plus standard chemotherapeutic regimens followed by anlotinib plus metronomic capecitabine as a maintenance therapy. Liver metastasectomy can be performed when liver metastases are converted to resectable lesions. The primary outcome was the investigator-confirmed objective response rate (ORR) in the intention-to-treat population. Among the 47 patients in Cohort A, the ORR was 40.4% (95% CI 26.4-55.7), including 1 with a complete response (CR) and 18 who achieved a partial response (PR). The median progression-free survival (PFS) was 8.7 months (95% CI 7.3-NE), and the median overall survival (OS) was not reached. In Cohort C, 14 of 44 patients achieved a PR, with an ORR of 31.8% (95% CI 18.6-47.6). The PFS and OS were 5.8 months (95% CI 4.8-6.5) and 11.4 months (95% CI 5.8-19.3), respectively. The liver metastasectomy rate in patients with liver-limited disease was 22.7% (5/22) in Cohort A and 6.7% (2/30) in Cohort C. For pancreatic cancer patients, the ORR of the efficacy-evaluable population was 36.0% (9/25), and those with liver-limited metastasis had better survival. Moreover, no new safety concerns emerged. In conclusion, an anlotinib-based first-line regimen demonstrated promising antitumor activity among GI cancer patients with unresectable liver metastases and led to liver metastasectomy in selected patients.
这项多队列II期试验（ALTER-G-001；NCT05262335）旨在评估一线安罗替尼联合化疗对伴有不可切除肝转移的胃肠道（GI）癌患者的疗效。符合条件的结直肠癌患者（队列A）或非结直肠癌和非食管癌的胃肠道癌患者（队列C）接受六个周期的安罗替尼联合标准化疗方案，随后接受安罗替尼联合节拍器剂量的卡培他滨作为维持治疗。当肝转移转化为可切除病变时可进行肝转移灶切除术。主要结局是意向性治疗人群中研究者确认的客观缓解率（ORR）。在队列A的47例患者中，ORR为40.4%（95%CI 26.4-55.7），包括1例完全缓解（CR）和18例部分缓解（PR）。中位无进展生存期（PFS）为8.7个月（95%CI 7.3-未达到），中位总生存期（OS）未达到。在队列C中，44例患者中有14例达到PR，ORR为31.8%（95%CI 18.6-47.6）。PFS和OS分别为5.8个月（95%CI 4.8-6.5）和11.4个月（95%CI 5.8-19.3）。在队列A中，肝局限性疾病患者的肝转移灶切除率为22.7%（5/22），在队列C中为6.7%（2/30）。对于胰腺癌患者，疗效可评估人群的ORR为36.0%（9/25），肝局限性转移患者的生存期更好。此外，未出现新的安全问题。总之，基于安罗替尼的一线方案在伴有不可切除肝转移的胃肠道癌患者中显示出有前景的抗肿瘤活性，并使部分患者能够进行肝转移灶切除术。
