Savolitinib Active, Tolerable in Subset of Advanced Papillary Renal Cell Cancer

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Savolitinib, a highly selective small molecule inhibitor of c-Met, was tolerable in a subgroup of patients with advanced PRCC.
Savolitinib, a highly selective small molecule inhibitor of c-Met, was tolerable in a subgroup of patients with advanced PRCC.

Savolitinib was active and tolerable in a subgroup of patients with advanced papillary renal cell carcinoma (PRCC), according to results from a phase 2 clinical trial published in the Journal of Clinical Oncology.

The agent is a highly selective small molecule inhibitor of c-Met, a single pass tyrosine kinase receptor encoded by the MET gene. Abnormal activation of MET is correlated with poor prognosis across cancer types.

This single-arm, phase II, multicenter study treated 109 patients with histologically confirmed advanced or metastatic PRCC with savolitinib 600 mg once daily. As aberrant activation of the MET pathway might drive PRCC, researchers evaluated safety and tolerability according to MET status.

MET-driven PRCC was defined as chromosome 7 copy gain, focal MET or HGF gene amplification, or MET kinase domain mutations.

In the 109 patients, PRCC was MET-driven in 40% (n=44) and MET-independent in 42% (n=46); 17% of patients (n=19) had unknown MET status.

Response to savolitinib strongly associated with MET-driven PRCC: Among patients with MET-driven disease, 18% experienced partial response, though no MET-independent patients experienced response (P =.002).

Median progression-free survival was 6.2 months (95% CI, 4.1-7.0) in MET-driven disease and 1.4 months (95% CI, 1.4-2.7) in MET-independent disease (hazard ratio, 0.33; 95% CI, 0.20-0.52; log-rank P <.001).

The most common treatment-related adverse events were nausea, fatigue, vomiting, and peripheral edema.

Reference

1. Choueiri TK, Plimack E, Arkenau HT, et al. Biomarker-based phase ii trial of savolitinib in patients with advanced papillary renal cell cancer [published online June 23, 2017]. J Clin Oncol. doi: 10.1200/JCO.2017.72.2967

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