Anlotinib was beneficial in Chinese patients with refractory metastatic colorectal cancer, with particular OS improvement among patients with RAS/KRAS/BRAF-wildtype, according to research presented at the virtual ASCO GI Cancers Symposium (J Clin Oncol 39, 2021 (suppl 3; abstr 65).

“The efficacy of late line treatments for metastatic colorectal cancer (mCRC) is still limited,” wrote Yihebali Chi, MD, PhD, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China, and colleagues, noting anlotinib is a multitarget TKI, mainly targeting VEGFR1-3.

Researchers conducted this phase 3 ALTER0703 trial to evaluate anti-tumor efficacy and safety of anlotinib monotherapy in refractory metastatic colorectal cancer.

A total of 421 patients with metastatic colorectal cancer, who had previously received at least 2 lines of chemotherapy, were enrolled between December 2014 and August 2016. Patients were randomly assigned 2:1 to receive anlotinib(n=282) or placebo(n=137) and were stratified by previous VEGF-targeting therapy and time from diagnosis to metastases.

The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate(ORR), disease control rate (DCR), safety and quality of life

The median OS by the cut-off date in August 2018 was 8.6 months in anlotinib which was not statistically an improvement over OS of 7.2 months in placebo. Median PFS was 4.1 months in anlotinib versus 1.5 months in placebo. Anlotinib improved ORR and DCR versus the placebo arm.

Two patients in the anlotinib arm experienced grade 5 treatment-related adverse events, both were hemorrhage.  Hypertension, increased y-GT, and hand-foot syndrome were the most common grade 3 anlotinib-related adverse events.

Notably, in a subset of patient with RAS/KRAS/BRAF wildtype, the median OS in anlotinib was 11.0 months, which was statistically prolonged versus OS of 6.7 months in the placebo arm.

“Anlotinib could provide clinical benefits by substantially prolonged PFS with manageable toxicity for Chinese refractory mCRC patients,” Dr Chi concluded in the presentation, highlighting further study could validate that anlotinib improves survival for patients with RAS/BRAF wildtype.—Kaitlyn Manasterski