SAN FRANCISCO (FRONTLINE MEDICAL NEWS)Famitinib, a novel oral anti-angiogenic agent, prolongs progression-free survival by 1.3 months in patients with metastatic colorectal cancer when given alone as third- or later-line therapy, in a randomized phase II trial .

“This trial reached its primary endpoint,” co–principal investigator Dr. Rui-hua Xu of Sun Yat-Sen University Cancer Center, Guangzhou, China, said at the annual Gastrointestinal Cancers Symposium, sponsored by the American Society of Clinical Oncology.

“Famitinib demonstrated a similar safety profile with other small-molecule anti-VEGFR [vascular endothelial growth factor receptor] agents,” he said.

There was no significant improvement in overall survival, however, although analyses suggested a possible trend toward benefit in the subset of patients with more heavily pretreated disease.

Invited discussant Dr. Wafik S. El-Deiry, professor and the Deputy Cancer Center Director for Translational Research at Fox Chase Cancer Center, Philadelphia, noted that the patients’ previous targeted therapies were not well described. “It is clear that a significant number of patients did get cetuximab [Erbitux] and bevacizumab [Avastin], but the breakdown was not mentioned,” he elaborated.

He compared the trial with the similar CORRECT trial, which led to approval by the Food and Drug Administration of regorafenib (Stivarga) for metastatic colorectal cancer. In that trial, regorafenib monotherapy yielded a progression-free survival benefit of 1.9 months, as well as an overall survival benefit.

“Subgroup analyses supported an impact of regorafenib on overall survival including KRAS-mutant colorectal cancer,” Dr. El-Deiry noted. “The lack of demonstrated efficacy on overall survival by famitinib may be aided if biomarkers are developed or if it is combined with other agents … I can’t overemphasize the need to develop and incorporate biomarkers so we can learn.

“Famitinib is not better in third line than approved regimens,” he concluded. “However, randomized comparisons or combination regimens may or may not in the future show improved or better outcomes. There is potential for pushing the doses.”

Patients were eligible for the trial if they had experienced failure of at least two prior lines of standard chemotherapy. They were ineligible if they had previously received a tyrosine kinase inhibitor targeting VEGF, had proteinuria or uncontrolled hypertension, or had a tendency for gastrointestinal bleeding.

A total of 154 patients were randomized in 2:1 ratio to double-blind treatment with either single-agent famitinib – a multitargeted tyrosine kinase inhibitor that mainly targets the vascular endothelial growth factor receptor 2 (VEGFR2), c-Kit, and the platelet-derived growth factor receptor (PDGFR) – or placebo, each taken once daily.

Results showed that median progression-free survival was 2.8 months with famitinib versus 1.5 months with placebo (hazard ratio, 0.59; P = .0053), Dr. Xu reported. Findings were similar across subgroups. There was no significant difference in overall survival, which stood at about 7.5 months in each group. The overall response rate was statistically indistinguishable between groups, but the famitinib group had a higher disease control rate (59% vs. 31%, P = .0016).

There was no significant difference in quality of life, according to Dr. Xu, who disclosed that he had no relevant conflicts of interest.

Patients treated with famitinib had a higher rate of grade 3 or worse drug-related adverse events (46% vs. 20%) and drug-related adverse events leading to treatment discontinuation (13% vs. 5%).

The main grade 3 or 4 adverse events in the famitinib group were hypertension (11%), thrombocytopenia (10%), hand-foot syndrome (10%), and neutropenia (9%).


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