In a randomized, multicenter phase 3 trial, the oral VEGFR tyrosine kinase inhibitor, anlotinib demonstrated comparable progression-free survival (PFS) and safety to bevacizumab, when combined with capecitabine and oxaliplatin (CapeOX), for treatment-naïve patients with unresectable RAS/BRAF wild-type metastatic colorectal cancer (mCRC).

These results were presented by Ke-Feng Ding, MD, PhD, Zhejiang University School of Medicine, Zhejiang, China, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting at Chicago, Illinois.

A combination of anti-VEGF antibodies and chemotherapy have been standard treatment for unresectable metastatic colorectal cancer (mCRC). However, research is limited on the impact of oral VEGFR-TKI combined with chemotherapy as treatment for RAS/BRAF wild-type mCRC.

Patients were randomized 1:1 to receive either anlotinib (12 mg daily, days 1–14) or bevacizumab (7.5 mg/kg IV, day 1) with oxaliplatin (130 mg/m² IV, day 1) and capecitabine (anlotinib group: 850 mg/m² BID; bevacizumab group: 1000 mg/m² BID, days 1–14) in 3-week cycles. After 4 to 8 cycles of induction therapy, patients continued maintenance therapy with their assigned VEGF inhibitor plus capecitabine until disease progression or unacceptable toxicity. Patients were stratified by tumor location and prior adjuvant chemotherapy.

The primary end point was PFS, while secondary end points included investigator-assessed PFS, overall response rate (ORR), disease control rate (DCR), duration of response (DoR), overall survival (OS), liver metastases resection rate, and quality of life.

Overall, 748 patients with RAS/BRAF wild-type mCRC were enrolled from May 2021 to August 2023. The median age was 59.0 years (interquartile range [IQR], 53.0 to 67.0) and most patients were male (69.65%). There were 373 patients in the anlotinib group and 375 patients in the bevacizumab group.

At a median follow-up of 25.1 months (95% confidence interval [CI], 23.82 to 26.25) and both patients in the anlotinib group and bevacizumab group demonstrated a median PFS of 11.04 months (95% CI, 9.82 to 11.17 and 95% CI, 9.69 to 11.17, respectively; hazard ratio [HR], 1.00; 95% CI, 0.84 to 1.18).

Patients who received anlotinib had a lower ORR (61.93%; 95% CI, 56.99 to 66.88) compared with patients who received bevacizumab (62.13%; 95% CI, 57.01 to 67.06). Additionally, the bevacizumab group demonstrated higher DCR (93.07%; 95% CI, 90.01 to 95.42 vs 92.76%; 95% CI, 89.64 to 95.18) and median DoR (9.69 months; 95% CI, 8.48 to 11.01 vs 9.66 months; 95% CI, 8.31 to 9.99) than patients in the anlotinib group. The resection rate of liver metastases was lower in the bevacizumab group than the anlotinib group (2.93% vs 3.75%).

Serious adverse events occurred in 38.3% of patients in the anlotinib group and 34.4% in the bevacizumab group, of which 73.99% were grade 3 or higher in the anlotinib group and 59.20% in the bevacizumab group.

"In unresectable RAS/BRAF wild-type mCRC patients, anlotinib plus CapeOX showed comparable PFS time and safety compared with bevacizumab plus CapeOX,” the researchers concluded, “The results provide a new treatment option for unresectable RAS/BRAF wild-type mCRC patients.”

Source:

Ding K, Liu Y, Zhang Y, et al. Anlotinib versus bevacizumab added to standard first-line chemotherapy among patients with RAS/BRAF wild-type, unresectable metastatic colorectal cancer: A multicenter, prospective, randomised, phase 3 clinical trial (ANCHOR trial). Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract LBA3502.