The investigational compound savolitinib appears to have antitumor activity in patients with c-MET-driven papillary renal cell carcinoma, according to the results of a phase II study released at the 2017 Genitourinary Cancers Symposium in Orlando, FL.
Savolitinib is an oral, highly selective inhibitor of the c-MET receptor tyrosine kinase.
Papillary renal cell carcinoma (RCC) is the second most common histologic subtype of RCC and is associated with c-MET gene alterations. C-MET and its ligand, hepatocyte growth factor, are known to play an important role in the molecular events underlying oncogenesis in papillary RCC.
Therapies that are currently available for patients with RCC produce only modest benefit in those with papillary RCC, and there are currently no therapies specifically approved to treat c-MET-driven papillary RCC.
Researchers at 22 sites across the United States, United Kingdom, Canada, and Spain tested the use of savolitinib in patients with papillary RCC, in whom anticancer activity was correlated with c-MET pathway alterations. Subjects had locally advanced or metastatic disease.
Overall, 109 study participants received at least one dose of savolitinib. Papillary RCC was c-MET-driven in 44 patients and c-MET-independent in 46 patients. C-MET status was unknown in 19 participants.
Results showed that c-MET status was more predictive of response to savolitinib than classification of papillary RCC based on pathology, reports principal investigator Toni Choueiri, director of the Lank Center for Genitourinary Oncology at the Dana Farber Cancer Institute in Boston, MA.
Savolitinib selectively inhibited c-MET-driven tumor progression in papillary RCC patients, with eight of the 44 patients (or 18 percent of the group) in this subgroup achieving a partial response.
Progression-free survival was 6.2 months in patients with c-MET-driven papillary RCC, compared with 1.4 months in patients with c-MET-independent disease, P < 0.0001.
Savolitinib treatment was generally well tolerated, and most adverse events were grade 1 or 2. The most common adverse events were nausea, fatigue, and vomiting.
A phase III study in patients with advanced papillary RCC is expected to start enrolling patients later this year.