Tivantinib is an effective second-line therapy for hepatocellular carcinoma (HCC) patients whose tumors exhibit high MET receptor tyrosine kinase expression, indicate phase II study results.
Furthermore, the findings indicate that expression of the MET proto-oncogene is an independent prognostic factor in patients who have failed to respond to first-line treatment.
"This study is the first randomised trial to identify a predictive biomarker that can be used to select patients who are most likely to benefit from treatment," say Lorenza Rimassa (Instituto Clinico Humanitas, Milan, Italy) and colleagues.
The study included 107 patients with unresectable, advanced-stage HCC, and Child-Pugh A or no liver cirrhosis, who had progressed on or were intolerant to previous systemic therapy. Patients received tivantinib 360 mg or 240 mg twice daily, or placebo until clinical or radiologic progression.
Overall, tivantinib resulted in an increased time to progression at 1.6 months compared with 1.4 months in the placebo group. However, survival did not significantly differ between the two groups (6.6 vs 6.2 months).
However, when the authors looked at subgroups, patients with high-MET tumors treated with tivantinib had significantly increased median time to progression at 2.7 months compared with 1.4 months in the placebo group. Furthermore, follow up showed that they had a 62% decreased risk for death, with a median survival of 7.2 months compared with 3.7 months for placebo-treated patients.
By contrast, there were no differences in efficacy between tivantinib- and placebo-treated patients with low-MET tumors.
The authors also noted that placebo-treated patients had a median survival of only 3.8 months if they had high-MET tumors compared with 9.0 months for patients with low-MET tumors ‑ further supporting the need for targeted therapy for this group of patients.
"The study provided clinically significant results based on independent radiological review and identified a biologically targeted population to be explored further in a phase 3 trial," Rimassa and colleagues conclude in The Lancet Oncology.
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