MET Inhibitor Savolitinib in Advanced Papillary Renal Cell Cancer

Key Points

  • Response to savolitinib was observed in 18% of patients with MET-driven disease vs 0% with MET-independent disease.
  • Median progression-free survival was 6.2 vs 1.4 months. 

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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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