- Tivantinib is a novel antitumor targeting agent that is a small molecule c-Met receptor tyrosine kinase inhibitor.
- In patients with non-small cell lung cancer (NSCLC) with high Met expression, patients in the combined Tivantinib group had significantly longer progression-free survival compared to erlotinib alone.
Tivantinib is a novel antitumor targeting agent that is a small molecule c-Met receptor tyrosine kinase inhibitor (tyrosine kinase inhibitor, TKI).
Tivantinib inhibits the activity of tyrosine kinases, protein kinases, and c-Met receptor tyrosine kinases in the c-Met target signaling pathway, and inhibits neovascularization for antitumor purposes.
Tivantinib can be used to treat a variety of tumors, mainly non-small cell lung cancer and gastrointestinal tumors.
Studies have found that Met and epidermal growth factor receptor (EGFR) appear to have synergistic effects on cell growth, and Met amplification is a common cause of EGFR TKI resistance.
So most clinical trials have combined Tivantinib with erlotinib, a first-generation EGFR-targeting agent, to enhance efficacy and prevent the development of resistance. It is currently in phase III clinical trials.
So, how well does Tivantinib work in NSCLC? Who are the patients with lung cancer for whom it is indicated? Let’s find out!
Tivaninib in combination with erlotinib extends survival in patients with refractory NSCLC
Back in 2010, a phase II clinical trial enrolling patients with advanced, refractory NSCLC showed that Tivantinib in combination with erlotinib prolonged progression-free survival (PFS). Patients in the combination Tivantinib group had a 66% longer median PFS compared to the combination placebo (16.1 weeks versus 9.7 weeks). After correction for a number of influencing factors, the difference between the two groups was even more pronounced, at 18.9 weeks versus 9.7 weeks, respectively.
Another phase I/II clinical trial in patients with NSCLC also corroborated this result, showing that patients in the Tivantinib combined with erlotinib group had a PFS of 26.3 weeks compared with 9.7 weeks with erlotinib alone
.
Met expression levels affect the effect of combination therapy
In July 2015, a multicenter phase III clinical study validated the efficacy and safety of Tivantinib in combination with erlotinib in patients with non-squamous NSCLC with varying Met expression levels who had locally progressed or metastasized after treatment.
The results of the study showed that:
(1) In patients with high Met expression, patients in the combination Tivantinib group had a PFS of 3.6 months compared with 1.6 months in the combination placebo group, with overall efficacy rates of 10.6% and 6.5%, respectively.
(2) In patients with low Met expression, the median overall survival (OS) was 8.5 months in the combination Tivantinib group and 7.8 months in the combination placebo group, with no significant difference. PFS and overall efficiency were higher in the combination Tivantinib group (PFS of 3.6 and 1.9 months and overall efficiency of 11.2% and 5.2%, respectively).
In terms of adverse reactions, the most common adverse events in the combination Tivantinib group were rash, diarrhea, weakness, or fatigue.
Tivantinib combined with erlotinib is more effective in EGFR-mutated advanced NSCLC
In a pivotal phase III study published in December 2017, investigators found that the combination of erlotinib + Tivantinib was equally effective in patients with advanced NSCLC with EGFR mutations, in addition to patients with NSCLC with Met mutations.
Patients in the combination of Tivantinib had significantly longer PFS compared with the single-agent arm (7.5 months and 13.0 months, respectively); median overall survival was 20.3 months and 25.5 months, respectively. Common adverse reactions included diarrhea, rash, and malaise.
Summary
Tivantinibi Although not yet available, several studies have shown that tivantinib in combination with erlotinib may be effective in patients with non-surgically resectable, locally advanced or metastatic non-squamous NSCLC, especially those with high MET expression.