Standard treatment for metastatic colorectal cancer (mCRC) typically involves antiangiogenic therapies, which block angiogenesis, the formation of new blood vessels, thereby starving cancer cells. Anlotinib, a multitarget tyrosine kinase inhibitor, works by targeting VEGFR1-3, which hinders tumor metastasis and growth. In study results to be presented this weekend at the 2021 Gastrointestinal Cancers Symposium, anlotinib demonstrated efficacy in patients with previously treated mCRC.
ALTER0703, a double-blinded, placebo-controlled phase 3 trial, enrolled 421 patients with metastatic colorectal cancer who had previously received at least 2 lines of chemotherapy. To be eligible, patients had to be aged 18 years or older, have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1, and have sufficient bone marrow, liver, and renal function. Patients were randomized in a 2:1 ratio to receive either anlotinib or placebo.
Although median overall survival was somewhat higher for anlotinib compared with placebo (8.6 vs 7.2 months), this difference was not statistically significant. However, median progression-free survival was significantly higher in the treatment group versus placebo (4.1 vs 1.5 months). In addition, for a subgroup of patients with RAS/KRAS/BRAF wild-type mCRC, median overall survival was significantly prolonged in the treatment arm versus placebo (11.0 vs 8.6 months).
Grade 3 or higher adverse events were reported in 52.5% of patients who received anlotinib compared with 19.7% of patients in the placebo group. Hypertension (20.9%), increased gamma-glutamyl transferase (GGT) (7.1%), and hand-foot syndrome (6.4%) were the most common grade 3 events experienced in the anlotinib group, but the side effects were resolved by decreasing the dose.
"Anlotinib could provide clinical benefits by substantially prolonged [progression-free survival] with manageable toxicity for Chinese refractory mCRC patients," write the researchers in their abstract, led by Yihebali Chi, MD, of the Cancer Institute and Hospital at the Chinese Academy of Medical Sciences, "although median [overall survival] did not reach significant improvement. Those with RAS/KRAS/BRAF wildtype might be the potential patients in anlotinib treatment."
For More Information
Chi Y, Shu Y, Ba Y, et al (2021). The efficacy and safety of anlotinib in refractory colorectal cancer: a double-blinded, placebo controlled, randomized phase III ALTER0703 trial. J Clin Oncol (Gastrointestinal Cancers Symposium Abstracts), 39(suppl_3). Abstract 65.
Image credit: Mikael Haggstrom, MD. Licensed under CC0