Colorectal cancer (CRC) is the third-most diagnosed cancer and second-leading cause of cancer deaths globally, with a high proportion of patients presenting with or progressing to metastatic disease. Among them, RAS/BRAF wild-type unresectable mCRC represents a challenging subset with poor long-term outcomes. Anlotinib, an oral antiangiogenic TKI targeting VEGFR, FGFR, and PDGFR pathways, has shown promise in this setting. Building on prior evidence of its efficacy with capecitabine/oxaliplatin (CAPEOX), the Phase III ANCHOR trial (NCT04854668) was designed to evaluate whether anlotinib plus CAPEOX is no inferior to bevacizumab plus CAPEOX as a first-line treatment in this population.

At a median follow-up of 25.10 months, the median Independent Review Committee (IRC)-assessed progression-free survival (PFS) was 11.04 months in both arms (HR 1.00; 95% CI 0.84 – 1.18), showing non-inferiority. 

The incidence of Grade ≥3 treatment-emergent adverse events (TEAEs) was higher with anlotinib (~74.0%) compared to bevacizumab (59.2%). Common TEAEs observed included hypertension, hand-foot syndrome, and diarrhea. Despite these adverse events, the rates of treatment discontinuation due to TEAEs were comparable between the two treatments, with anlotinib at 8.0% and bevacizumab at 9.1%. Additionally, TEAE-related deaths were slightly lower in the anlotinib group (~4.3%) compared to bevacizumab (4.5%).

KOL insights

“Anlotinib plus CapeOX demonstrated similar antitumor activity compared with bevacizumab plus CapeOX in the first-line treatment of RAS/BRAF wild-type mCRC, with a manageable safety profile and comparable health-related quality of life. The intravenous-free maintenance strategy of anlotinib and capecitabine may largely increase the compliance and convenience for patients with mCRC” – Expert Opinion

“Multi-targeted TKIs [such as anlotinib] that mainly target VEGFR are currently standard regimens for refractory mCRC, offering oral convenience, flexible dosing, and cost advantages,”– Expert Opinion

“Anlotinib plus CapeOX demonstrated similar antitumor activity compared with bevacizumab plus CapeOX in the first-line treatment of RAS/BRAF wild-type mCRC, with a manageable safety profile and comparable health-related quality of life,”– Expert Opinion

Conclusion

The standard first-line treatment for unresectable mCRC includes anti-VEGF antibodies in combination with chemotherapy. However, there were no prior randomized trials assessing the combination of VEGFR-TKIs with chemotherapy in  first-line. 

The purpose of the ANCHOR trial was to evaluate whether anlotinib plus CapeOX is no worse than bevacizumab plus CapeOX in treating RAS/BRAF wild-type mCRC. Anlotinib plus CapeOX was non-inferior to bevacizumab plus CapeOX in the first-line treatment of RAS/BRAF wild-type metastatic colorectal cancer, offering similar clinical benefits in terms of disease control and response. The oral formulation of anlotinib adds a potential advantage in terms of patient convenience and adherence, positioning it as a viable and practical alternative to bevacizumab in this setting. The safety profile of anlotinib may limit its widespread adoption despite its oral administration advantage because high-grade adverse events were more frequent with anlotinib.