Savolitinib, a potent and selective small-molecule MET kinase inhibitor, was tolerable, safe, and may have treatment potential for patients with MET-driven papillary renal cell carcinoma (PRCC), according to a trial published in the Journal of Clinical Oncology.1
Metastasis, angiogenesis, tumor growth, and treatment resistance are each associated with MET activation and lead to a poor prognosis in many cancers. The primary objective of this study was to determine savolitinib activity in PRCC tumors by MET status.
This single arm, phase 2 study (ClinicalTrial.gov ID: NCT02127710) enrolled 109 patients and assessed the safety and efficacy of savolitinib in patients with histologically confirmed locally advanced or metastatic PRCC. Forty percent of patients had MET-driven PRCC, 42% were MET-independent, and 17% had unknown MET status. Patients received savolitinib 600 mg once daily.
The overall response rate (ORR) was 7% in the treatment population, but MET-driven patients had a significantly higher response rate of 18% partial response vs MET-independent PRCC (0%).
Patients with MET-driven PRCC had a median progression-free survival (mPFS) of 6.2 months (95% CI: 4.1-7.0) vs 1.4 months in MET-independent PRCC (95% CI: 1.4-2.7), (hazard ratio [HR], 0.33; 95% CI: 0.20-0.52; log-rank P < .001).
The most frequently observed adverse effects in patients were nausea, vomiting, fatigue, and peripheral edema.
Study authors concluded that “these results confirm that savolitinib, a potent and selective small-molecule MET kinase inhibitor, holds promise as a personalized treatment for patients with metastatic MET-driven PRCC.”
- Choueiri TK, Plimack E, Arkenau HT, et al. Biomarker-based phase II trial of savolitinib in patients with advanced papillary renal cell cancer. J Clin Oncol. 2017 Jun 23. doi: 10.1200/JCO.2017.72.2967 [Epub ahead of print]