Abstract
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.