A phase II multicenter study, ALTER-G-001, investigated the efficacy and safety of anlotinib in combination with chemotherapy as a first-line treatment for patients with advanced gastrointestinal (GI) cancers and unresectable liver metastasis. The study, published in Nature, enrolled patients with stage IV colorectal cancer (CRC) and other GI cancers, excluding esophageal squamous cell carcinoma (ESCC). The results suggest that the combination therapy may offer a potential new treatment option for these patients.
Study Design and Patient Population
The ALTER-G-001 trial was a phase II, multicenter, single-arm, investigator-initiated exploratory study. It enrolled adult patients aged 18 to 75 years with histologically or cytologically confirmed GI cancer and unresectable liver metastasis. Cohort A consisted of patients with stage IV CRC, while Cohort C included patients with GI cancers other than CRC and ESCC, such as gastric cancer, pancreatic cancer, and biliary tract cancer. Key eligibility criteria included an ECOG performance status of 0-1 and adequate organ function. Patients had not received prior systemic therapy.
Treatment Regimens
In Cohort A, patients received 12 mg oral anlotinib daily on days 1-14 of each cycle, combined with the CAPEOX regimen (capecitabine and oxaliplatin). Cohort C received 12 mg oral anlotinib daily on days 1-14 of each cycle plus standard-of-care (SOC) chemotherapy at the investigator's discretion. Each cycle lasted three weeks. After six cycles of induction therapy, patients eligible for surgery underwent resection. Patients who achieved disease control (CR, PR, or SD) and were ineligible for surgery received maintenance therapy with anlotinib and metronomic capecitabine (Cohort A) or anlotinib plus chemotherapy (Cohort C).
Efficacy Outcomes
The primary endpoint was investigator-confirmed objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DoR), and the conversion rate of liver metastasis to resectability. Statistical analysis was performed using SAS version 9.4, with a p-value < 0.05 considered statistically significant.
Safety Profile
The occurrence, frequency, and severity of adverse events (AEs) were assessed throughout the treatment period using the National Cancer Institute Common Terminology Criteria of Adverse Events (NCI CTCAE) version 5.0. The incidence of perioperative treatment-emergent adverse events (TEAEs) was assessed from the end of systemic treatment to 30 days after surgery. Serious AEs were observed and monitored throughout the study.
Promising Results Warrant Further Investigation
The results of the ALTER-G-001 trial suggest that anlotinib in combination with chemotherapy shows promise as a first-line treatment for advanced GI cancers with unresectable liver metastasis. The combination therapy demonstrated encouraging ORR and DCR in both CRC and other GI cancer cohorts. The safety profile was manageable, with AEs being monitored and managed according to established guidelines. These findings warrant further investigation in larger, randomized controlled trials to confirm the efficacy and safety of this combination therapy and to determine its role in the treatment of advanced GI cancers.
