Anlotinib plus sintilimab as first-line treatment for patients with advanced colorectal cancer (APICAL-CRC): an open-label, single-arm, phase II trial.

This is an investigator-initiated, open-label, single-arm, phase II trial that aimed to assess the combination of sintilimab plus anlotinib among patients with treatment-naïve metastatic colorectal cancer (mCRC) (APICAL-CRC ClinicalTrials.gov number, NCT04271813). Between June 2020 and September 2023, a total of 30 patients were eventually enrolled and received the study regimen. Among these 30 patients, 50% had an Eastern Cooperative Oncology Group(ECOG) score of 0-1, and the other 50% had a score of 2. The objective response rates (ORRs) were 48.3% (95% CI 29.4-67.5) in the efficacy-evaluable cohort and 46.7% (95% CI 28.3-65.7) in the intent-to-treat (ITT) cohort. Twelve patients had stable disease, and the disease control rates (DCRs) were 89.7% (95% CI 72.6-97.8) and 86.7% (95% CI 69.3-96.2) in the efficacy-evaluable and ITT cohorts, respectively. The median progression-free survival (mPFS) was 8.6 months (95% CI 4.8-11.0), and the median overall survival (mOS) reached 22.9 months (95% CI 13.5-36.3). Treatment-related adverse events (TRAEs) of any grade were reported in 23 patients (76.7%), and grade 3 TRAEs occurred in 4 patients (13.3%). Multivariate Cox regression analysis revealed that the presence of liver metastases was an independent prognostic factor for poor PFS (HR = 5.66, 95% CI 1.58-20.2) and OS (HR = 7.85, 95% CI 1.38-44.8), whereas FLT mutation was independently associated with poor OS(HR = 12.5, 95% CI 1.54-101). This trial demonstrated that sintilimab plus anlotinib exhibited promising antitumor efficacy along with a manageable safety profile among treatment-naïve mCRC patients.