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肝转移不可切除的胃肠道 （GI） 癌症患者的疗效。符合条件的结直肠癌患者（队列 A）或非结直肠和非食管胃肠道癌患者（队列 C）接受了六个周期的安罗替尼加标准化疗方案，然后接受安罗替尼加节律卡培他滨作为维持治疗。当肝转移瘤转化为可切除的病灶时，可以进行肝转移灶切除术。主要结局是意向治疗人群中研究者确认的客观缓解率 （ORR）。在队列 A 的 47 名患者中，ORR 为 40.4% （95% CI 26.4-55.7），包括 1 名完全缓解 （CR） 和 18 名达到部分缓解 （PR）。中位无进展生存期 （PFS） 为 8.7 个月 （95% CI 7.3-NE），未达到中位总生存期 （OS）。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）。队列 A 和队列 C 中肝脏局限性疾病患者的肝转移切除术率分别为 22.7% （5/22） 和 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率更高。此外，没有出现新的安全问题。总之，基于安罗替尼的一线方案在肝转移不可切除的胃肠道癌症患者中显示出有希望的抗肿瘤活性，并导致特定患者进行肝转移切除术。