Anlotinib non-inferior to bevacizumab in first-line treatment of mCRC

A large, multicentre phase 3 trial has demonstrated that anlotinib, an oral multi-target tyrosine kinase inhibitor (TKI), is non-inferior to bevacizumab when each is combined with capecitabine and oxaliplatin (CAPOX) in the first-line treatment of RAS/BRAF wildtype, unresectable metastatic colorectal cancer (mCRC). These findings may expand treatment options for patients by offering an effective oral anti-angiogenic alternative to intravenous anti-VEGF therapy.

The open-label ANCHOR trial (NCT04854668), presented by Dr Ke-Feng Ding (Zhejiang University School of Medicine, Hangzhou, China), randomised treatment-naïve patients with confirmed RAS/BRAF wildtype mCRC and multidisciplinary team (MDT)-determined unresectable metastases (n=748) 1:1 to receive either anlotinib or bevacizumab alongside CAPOX [1,2]. Anlotinib is a multi-targeted TKI that inhibits VEGFR 1/2/3, FGFR 1–4, and PDGFR α/β. The primary endpoint was progression-free survival (PFS), as assessed by an independent review committee (IRC), with a non-inferiority margin of HR ≤1.09.

After a median follow-up of 25.1 months, both treatment arms demonstrated an identical median PFS of 11.04 months (HR 1.00; 95% CI 0.84–1.18). These results met the predefined criteria for non-inferiority. “This is the first randomised trial to directly compare an oral VEGFR-TKI to bevacizumab in combination with chemotherapy in this setting,” said Dr Ding. “The findings show that anlotinib offers comparable disease control and PFS with a manageable safety profile.”

In terms of safety, serious adverse events were reported in 38.3% of participants in the anlotinib group and 34.4% in the bevacizumab group. The safety profiles were consistent with known toxicities of VEGF pathway inhibition, with no new safety concerns raised. The capecitabine dose was slightly reduced in the anlotinib arm (850 mg/m² vs 1000 mg/m²) to mitigate toxicity during the oral combination. Secondary endpoints included overall survival, objective response rate, disease control rate, and rate of liver metastases resection, which are still under evaluation. However, initial analysis shows broadly similar performance between arms.

Anti-VEGF monoclonal antibodies currently remain the standard anti-angiogenic agents used in combination with chemotherapy for the treatment of mCRC. However, the ANCHOR trial opens the door to oral regimens, particularly in settings where intravenous access is limited or patient convenience is a priority. “Having an oral alternative to bevacizumab could improve treatment accessibility and reduce the burden of intravenous therapy for patients,” Dr Ding commented. “These results support the use of anlotinib as a frontline anti-angiogenic partner in RAS/BRAF wildtype mCRC.”

The trial reinforces the growing body of evidence that RAS/BRAF wildtype mCRC represents a biologically distinct subgroup that may benefit from precision-tailored approaches. Patients with microsatellite instability-high (MSI-H) or mismatch repair deficiency were excluded, as immunotherapy remains the preferred first-line option for that population [2].

1. Ding, KF, 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). Abstract 485208, ASCO Annual Meeting 2025, 30 May–3 June, Chicago, IL, USA.
2. He J, et al. Technol Cancer Res Treat. 2023;22:15330338231152350.

Medical writing support was provided by Dr Rachel Giles.
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Posted on 3 June 20254 June 2025