MET Inhibitor Savolitinib in Advanced Papillary Renal Cell Cancer
In a biomarker-based phase II trial reported in the Journal of Clinical Oncology, Choueiri et al found that the MET tyrosine kinase inhibitor savolitinib was active in MET-driven advanced papillary renal cell cancer.
Study Details
In the trial, 109 patients with locally advanced or metastatic disease received savolitinib at 600 mg orally once daily. MET-driven disease was defined as chromosome 7 copy gain, focal MET or HGF gene amplification, or MET kinase domain mutations.
Overall, 98% of patients had metastatic disease, 45% had prior systemic therapy, 73% had undergone nephrectomy, 20% had prior radiotherapy, and 26% had received sunitinib (Sutent). papillary renal cell cancer was MET-driven in 40% of patients, MET-independent in 42%, and of unknown MET status in 17%. The primary objective was to assess efficacy according to MET status.
Responses
Objective response was observed in 8 patients (18%, all partial responses) with MET-driven disease vs none of the patients (0%) with MET-independent disease (P = .002). Durations of response were 2.4 to 16.4 months in 6 responders still responding at data cutoff and 1.8 to 2.8 months in the remaining 2 responders. In an analysis according to histologic subtype, response was observed in 2 of 12 patients (17%) with type 1 and 1 of 23 patients (4%) with type 2 papillary renal cell cancer; 5 responders were not classified as having either type 1 or 2 disease on central review. Stable disease was observed in 50% vs 24% of patients. Median progression-free survival was 6.2 months vs 1.4 months (hazard ratio = 0.33, P < .001). Patients with unknown MET status had a response rate of 0%.
Adverse Events
Grade ≥ 3 adverse events occurred in 47% of patients and were considered related to treatment in 19%. The most common treatment-related adverse events of any grade were nausea (39%), fatigue (19%), vomiting (17%), and peripheral edema (16%). Serious adverse events occurred in 21%, and adverse events led to discontinuation of treatment in 8%.
The investigators concluded: “These data show activity and tolerability of savolitinib in the subgroup of patients with MET-driven [papillary renal cell cancer]. Furthermore, molecular characterization of MET status was more predictive of response to savolitinib than a classification based on pathology. These findings justify investigating savolitinib in MET-driven [papillary renal cell cancer].”
The study was supported by AstraZeneca.
Toni K. Choueiri, MD, of Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.
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