Frontline Anlotinib Plus CapeOX Elicits Similar Efficacy to SOC Therapy in RAS/BRAF Wild-Type mCRC

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Ashling Wahner & MJH Life Sciences Using AI

The frontline combination of anlotinib and capecitabine/oxaliplatin (CapeOX) was noninferior to bevacizumab (Avastin) plus CapeOX regarding progression-free survival (PFS) in patients from China with RAS/BRAF wild-type, unresectable metastatic colorectal cancer (mCRC), according to findings from a phase 3 trial (NCT04854668).

Data presented at the 2025 ASCO Annual Meeting showed that the median PFS, as assessed by an independent review committee (IRC), was 11.04 months for both anlotinib (95% CI, 9.82-11.17) and bevacizumab (95% CI, 9.69-11.17), with a hazard ratio for noninferiority of 1.00 (95% CI,0.84-1.18; stratified log-rank P =.8740), meeting the primary end point of the trial. Also per IRC review, the objective response rate (ORR) was 61.93% (95% CI, 56.79%-66.88%) and 62.13% (95% CI, 57.01%-67.06%; P =.9487), and the disease control rate (DCR) was 92.76% (95% CI, 89.64%-95.18%) and 93.07% (95% CI, 90.01%-95.42%; P =.8681) for the anlotinib and bevacizumab arms, respectively.

The median duration of response (DOR) was 9.66 months (95% CI, 8.31-9.99) with anlotinib vs 9.69 months (95% CI, 8.48-11.01) with bevacizumab (HR, 1.04; 95% CI, 0.84-1.27). Additionally, the resection rate of liver metastases was also similar at 3.75% vs 2.93%, respectively (P =.5327).

Safety showed that although all-grade treatment-related adverse events (TRAEs) were comparable between the study arms (98.12% vs 97.87% in the anlotinib vs bevacizumab arms, respectively), grade ≥3 TRAEs were higher in the anlotinib arm at 64.88% vs 44.80%, respectively. Accordingly, dose reductions caused by TRAEs were also higher in the anlotinib arm at 47.18% vs 33.87%, respectively.

Despite this variance in high-grade TRAE incidence, Ke-Feng Ding, MD, PhD, stressed that these TRAEs were highly manageable, as evidenced by similar rates of TRAEs leading to treatment discontinuation (2.14% in the anlotinib arm vs 2.93% in the bevacizumab arm) and a similar number of TRAEs leading to death (6 vs 4 in the 2 groups, respectively). Along this line, Ding highlighted that quality of life was also comparable between the study arms, with “no significant difference in the longitudinal score changes of the EQ-5D VAS and GHS.”

“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,” said Ding when presenting the data at the ASCO. Ding works in the Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, in Hangzhou, China.

Study Background and Patient Characteristics

Explaining the rationale for the multicenter, noninferiority phase 3 ANCHOR trial, Ding said, “Anti-VEGF antibodies [such as bevacizumab] combined with chemotherapy remain first-line treatment for unresectable mCRC, but no randomized trials have evaluated oral VEGFR-[tyrosine kinase inhibitor (TKI)] plus chemotherapy in this setting.”

“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,” added Ding.

The intention-to-treat (ITT) population for ANCHOR included 748 patients with previously untreated RAS/BRAF wild-type mCRC and unresectable metastases diagnosed by a multidisciplinary team. Patients were randomized and treated at multiple clinical sites in China between May 25, 2021, and August 30, 2023.

Patient characteristics were well balanced between the 2 study cohorts. Across the entire ITT population, the median age was 59 years (range, 24-75), with one-third of patients aged ≥65 years. Seventy percent of the patients were male, and 70% had an ECOG performance status of 1. The primary tumor location for 85.29% of patients was the left side of the colon and rectum. About three-fourths (73.66%) of patients had at least some liver metastases, with one-fourth (25.13%) having liver-only metastases. Half of the patients had undergone resection of their primary tumor, and 18.58% had received prior adjuvant chemotherapy.

In the experimental arm (n = 373), patients received the oral multikinase inhibitor anlotinib at 12 mg daily on days 1-14 plus CapeOX in 3-week cycles. In this group, capecitabine at 850 mg/m2 was given orally twice daily on days 1-14, and oxaliplatin was administered at 130 mg/m² (IV) on day 1. Patients were treated in 3-week cycles. In the control arm (n = 375), patients received the anti-VEGF antibody bevacizumab (7.5 mg/kg [IV] on day 1) plus oxaliplatin 130 mg/m² [IV] day 1) and capecitabine (1000 mg/m² orally twice daily on days 1-14). These patients were also treated in 3-week cycles. Following 4 to 8 induction cycles, patients in the experimental and control arms received maintenance treatment with anlotinib or bevacizumab, respectively, both combined with capecitabine, until unacceptable toxicity or disease progression.

The primary end point of the trial was PFS per IRC with a hazard ratio for noninferiority benchmark of ≤1.09. Secondary end points comprised PFS, ORR, DCR, DOR, overall survival, liver metastases resection rate, quality of life, and safety.

In his concluding remarks, Ding again highlighted the significance of the maintenance regimen in the anlotinib arm being completely oral.

“The totally intravenous-free maintenance strategy of anlotinib and capecitabine may largely increase the compliance and convenience for [patients with] mCRC,” said Ding.

Reference

Ke-Feng D, 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). J Clin Oncol. 2025;43(suppl 17):LBA3502. doi:10.1200/JCO.2025.43.17_suppl.LBA3502