420P - A single-arm, multicenter, phase II study of anlotinib combined with CAPEOX as first-line treatment in RAS/BRAF wild-type unresectable metastatic colorectal cancer (ALTER-C002)

Background

Anlotinib is an oral multi-target tyrosine kinase inhibitor, mainly targets VEGFR1-3, FGFR 1-4, PDGFR α/β and c-kit. Previous trial has demonstrated that anlotinib monotherapy was effective and safe in advanced colorectal cancer following the failure of standard treatment. ALTER-C002 trial was designed to evaluate the efficacy and safety of anlotinib plus CAPEOX as first-line therapy in patients with RAS/BRAF wild-type unresectable metastatic colorectal cancer (mCRC). Preliminary results demonstrated significant antitumor activity and manageable toxicity. Here we updated the results at the data cutoff of Apr 30, 2021.

Methods

Patients with RAS/BRAF wild-type unresectable mCRC and no prior systemic treatment received anlotinib (12 mg p.o. qd, on day1-14 every 3 weeks), capecitabine (850 mg/m² p.o., bid, on day 1-14 every 3 weeks) and oxaliplatin (130 mg/m² i.v., on day 1 every 3 weeks) for 6 cycles followed by anlotinib and capecitabine maintenance until disease progression. Tumor response was assessed every 6 weeks according to RECIST v1.1 by investigator. The primary endpoint was ORR, and secondary endpoints included safety, DCR, DOR and PFS.

Results

From Nov 2019 to Feb 2021, 30 eligible patients were enrolled, of whom, median age was 60y (range, 32-72y), 26 (86.7%) had left colon or rectal cancer, and 24 (80.0%) had liver metastases. The ORR was 73.3% (95% CI, 54.1-87.7%) with 1 patient achieved a complete response (CR); DCR was 100% (95% CI, 88.4-100.0%). 2 patients received radical surgery after treatment; 12 patients had ongoing responses at data cutoff. Grade 3-4 treatment-emergent adverse events (TEAEs) occurred in 22 (73.3%) patients; the most common (≥10%) TEAEs were hypertension (46.7%, 14/30 pts), neutropenia (26.7%, 8/30 pts) and diarrhea (13.3%, 4/30 pts). No grade 5 treatment-related events occurred.

Conclusions

Anlotinib combined with CAPEOX achieved higher ORR in the first-line treatment of mCRC compared to those of previous treatment. Longer follow-up is needed for more complete assessment, and we’re launching a phase III, multicenter, double-blind trial to further assess the efficacy of this regimen.

Clinical trial identification

NCT04080843.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.