Savolitinib for MET-driven papillary renal cell carcinoma.

Abstract

Patients with advanced papillary renal cell carcinoma harbouring MET alterations could respond to treatment with the selective MET tyrosine kinase inhibitor savolitinib, according to the results of a recent clinical trial. Papillary renal cell carcinoma has few effective treatment options. MET alterations (kinase domain mutations or gene amplification) are un common in these carcinomas, and the associated activation of the MET pathway is thought to drive tumour growth. In the single-arm, inter national, phase 2 study by Toni Choueiri (Dana-Farber Cancer Institute, Boston, MA, USA) and colleagues, 109 patients with locally advanced or metastatic papillary renal cell carcinoma were given savolitinib (600 mg orally once daily); clinical tumour samples from each patient were assessed for MET alterations with a next-generation sequencing assay. The activity of savolitinib was strongly asso ciated with the presence of MET alterations in the tumour. Eight (18%) of the 44 patients with MET-driven tumours achieved objective responses (all confirmed partial responses) to savolitinib, whereas no responses were recorded in the 46 patients whose tumours were MET-independent (p=0·002). Furthermore, patients with METdriven tumours had a longer median progression-free survival than those with MET-independent tumours (6·2 months [95% CI 4·1–7·0] vs 1·4 months [1·4–2·7]; hazard ratio 0·33 [95% CI 0·20–0·52]; log-rank p<0·001). Savolitinib had a tolerable safety profile, with the most frequent drugrelated adverse events being nausea, vomiting, and peripheral oedema. Choueiri commented on savolitinib: “Perhaps this drug makes the most sense in a subset of papillary renal cell cancer patients with MET alterations. Molecular characterisation by MET status was more predictive of response to savolitinib than pathology.” Choueiri added that an international, phase 3 trial is planned to test sunitinib versus savolitinib only in patients with MET alterations. Hans Hammers (UT Southwestern Medical Center, Dallas, TX, USA) said the study results were encouraging: “The problem with kidney cancer is that we really have not had a good biomarker to select for treating patients.” Although the results will need confirmation in a phase 3 trial, he added: “For the first time, we would identify a molecularly identifiable subset of patients, and we can deliver a therapy that may be more effective in this population than the current standard of care.”

DOI: 10.1016/S1470-2045(17)30508-9

Cite this paper

@article{Gilbert2017SavolitinibFM, title={Savolitinib for MET-driven papillary renal cell carcinoma.}, author={Judith A. Gilbert}, journal={The Lancet. Oncology}, year={2017}, volume={18 8}, pages={e440} }