Rui-hua Xu, MD
Treatment with a multitargeted tyrosine kinase inhibitor led to a small but statistically significant improvement in progression-free survival (PFS) in patients with advanced, previously treated metastatic colorectal cancer, Chinese investigators reported at the 2015 Gastrointestinal (GI) Cancers Symposium.
In a phase II study, famitinib monotherapy was associated with a median PFS of 2.8 months compared with 1.5 months in patients treated with placebo (P
= .0040). Subgroup analysis showed a similar PFS advantage in favor of famitinib irrespective of sex, patient age, or extent of metastatic involvement.
Overall survival, a secondary endpoint, did not differ between treatment groups, lead study author Rui-hua Xu, MD, reported at the GI symposium.
“Famitinib, as a single-agent treatment, improved the PFS by 1.3 months in patients with advanced/metastatic colorectal cancer,” said Xu, a medical oncologist at Sun Yat-Sen University Cancer Center in Guangzhou, China. “Famitinib demonstrated a similar safety profile with other molecular anti-VEGFR agents. The most common adverse events were neutropenia, thrombocytopenia, proteinuria, hypertension, and hand-foot syndrome, which were tolerable and manageable.
“No statistical difference was observed in median overall survival, but a trend toward prolonged median overall survival was noticed in the subgroup of patients who had completed more cycles of therapy. Further study in this population is warranted.”
Patients with advanced/metastatic colorectal cancer have few effective treatment options. In China, standard first- and second-line chemotherapeutic regimens are FOLFOX and FOLFIRI. Cetuximab and bevacizumab are the only targeted agents approved for treatment of advanced/metastatic colorectal cancer.
Targeting tumor angiogenesis, famitinib is a small-molecule inhibitor of VEGFR2, c-Kit, and PDGFR. Xu and colleagues sought to determine in a multicenter trial whether famitinib could improve PFS in patients with advanced colorectal cancer that had progressed through at least two prior lines of chemotherapy.
Investigators randomized 154 patients in 2:1 ratio to faminitib or placebo, and treatment continued until disease progression or development of unacceptable toxicity. The patients had a median age of about 55 years, and 60% had received more than three prior lines of therapy. More than 40% of the patients had a treatment history that included exposure to antibody therapy.
When the trial ended, the results demonstrated a 40% reduction in the hazard for progression or death (HR = 0.0596; P
= .0053). Two patients in the famitinib group achieved partial responses and 53 had stable disease, resulting in a disease control rate of 59.8%. No objective responses were observed in the placebo group, and 16 patients had stable disease, leading to a disease control rate of 31.4% (P
In general, famitinib was well tolerated. Half the patients in the famitinib group had grade 3 or higher adverse events, most of which were considered drug related. The most frequently reported grade ≥3 adverse events in the famitinib arm were hypertension (11.1%), thrombocytopenia (10.1%), hand-foot syndrome (10.1%), diarrhea (10.1%), and neutropenia (9.1%).
Rates of serious drug-related adverse events were 5.1% and 3.6% in the famitinib and placebo groups, respectively. Discontinuation rates secondary to adverse events were 14% with famitinib and 5.5% with placebo.
Xu R-H, Shen L, Wang K, et al. A randomized, double-blind, parallel-group, placebo-controlled, multicenter, phase II clinical study of famitinib in the treatment of advanced metastatic colorectal cancer. Presented at: 2015 Gastrointestinal Cancers Symposium; January 15-17, 2015; San Francisco, CA. Abstract 513.
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