Savolitinib, a selective inhibitor of the MET tyrosine kinase pathway, demonstrates activity and tolerability in patients with papillary renal cell cancer (pRCC), according to data published in the Journal of Clinical Oncology.

Although clear cell RCC is the most common histological subtype of renal tumour, the papillary variant comprises ∼40% of non-clear cell tumours, with an estimated incidence of ∼6,400 cases per year in the USA. The papillary subtype can be further subclassified; type 1 pRCC tumours are characterized by mutations in the MET receptor tyrosine kinase gene. Activation of the MET pathway promotes tumour growth, angiogenesis, and metastasis; thus, inhibition of this pathway could offer a therapeutic target for this hard-to-treat disease.

Choueiri and colleagues carried out a single-arm, multicentre, global, phase II study to evaluate the efficacy and tolerability of savolitinib in patients with pRCC. Participants (n = 109) received 600 mg of oral savolitinib daily, until RECIST-defined progression or discontinuation criteria were met.

Using next-generation sequencing with a 400-gene panel, tumours were confirmed as MET-positive if MET copy number gain, HGF gene amplification, or MET kinase domain mutations were identified (n = 44). MET-driven pRCC was strongly associated with response to savolitinib: eight partial responders were observed in the MET-driven group, versus none in the MET-independent group (P = 0.002). Median progression-free survival for patients with MET-driven pRCC was 6.2 months, versus 1.4 months for those with MET-independent pRCC. 75% of the patients who showed a partial response were still responsive at the study cut-off point, demonstrating an enduring response. 88% of participants experienced ≥1 adverse effect of therapy, but most events were low-grade, including nausea and vomiting, fatigue, and peripheral oedema.

Overall, these data support the further study of savolitinib for pRCC driven by MET and, indeed, a phase III trial has recently been launched.