Crizotinib Shows Activity in Advanced Papillary RCC With MET Mutation

Treatment with crizotinib resulted in objective responses and long-lasting disease control in patients with advanced papillary renal cell carcinoma type 1 with MET mutations or amplification, according to the results of a phase II study published in the European Journal of Cancer.

“Objective, durable responses were observed in two of four (50.0%) patients with predefined mutations of the MET gene,” wrote Patrick Schöffski, MD, MPH, of the Leuven Cancer Institute in Belgium, and colleagues.

The small study included 23 patients with confirmed pathology. Four patients were MET mutation–positive. All patients received 250 mg oral crizotinib twice daily. The primary endpoint was objective response rate (ORR).

“The median duration of treatment and the median number of treatment cycles in the MET-positive subgroup were three times higher than in the MET-negative subgroup (48.6 vs 15.0 weeks or 16.5 vs 5.0 cycles, respectively), which likely reflects selective effects of the experimental treatment in different genetically defined subsets of this disease,” the researchers noted.

In the four patients with MET-positive disease, two achieved partial response and one had stable disease (ORR, 50%). The duration of response was 21.8 months and 37.3 months, respectively. The patient with a duration of response of 37.3 months eventually progressed. The 1-year progression-free survival rate was 75.0%, and the 1-year overall survival rate was 75.0%.

There were 16 patients with MET-negative disease, of whom one achieved a partial response lasting more than 9.9 months, and 11 had stable disease (ORR, 6.3%). The 1-year progression-free survival rate was 27.3%, and the 1-year overall survival rate was 71.8%.

Additionally, three patients had unknown MET status because of a technical failure. In these patients, one achieved partial response lasting more than 6.9 months and one had stable disease (ORR, 33.3%).

The most common treatment-related adverse events were edema (47.8%), fatigue (47.8%), nausea (39.1%), diarrhea (39.1%), and blurred vision (34.8%).

A post-hoc analysis identified MET amplification in one patient with MET-positive disease, who had a partial response and a duration of response of more than 3 years, and in one patient with MET-negative disease who achieved stable disease.

“When combining cases with either MET mutation or amplification in a post-hoc analysis, all patients achieved stable disease or an objective response, with 80% of these patients being progression-free at 1 year after the start of crizotinib treatment,” the researchers wrote. “The duration of disease stabilization in patients without MET mutation or amplification was generally shorter and only one among 16 MET-negative patients achieved a confirmed RECIST partial response.”