Savolitinib has potential in MET-driven papillary RCC
medwireNews: Savolitinib, a highly selective MET tyrosine kinase inhibitor, shows activity in patients with MET-driven advanced papillary renal cell carcinoma (PRCC), researchers report.
Toni Choueiri (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and colleagues say the findings of their phase II study justify further investigation of savolitinib in MET-driven PRCC.
For the study, 109 patients with histologically confirmed locally advanced or metastatic PRCC received oral savolitinib (AZD6094, HMPL-504, volitinib) 600 mg once daily. Of these patients, 44 (40%) had MET-driven PRCC, defined by the presence of chromosome 7 MET copy number gain, focal MET or HGF gene amplification, or MET kinase domain mutations in their tumor samples. A further 46 (42%) patients had MET-independent PRCC and 19 (17%) had unknown MET status.
As reported in the Journal of Clinical Oncology, the overall objective response rate (ORR) was 7%. However, when the researchers analyzed the data according to MET status, they found that the ORR was significantly higher in patients with MET-driven PRCC than in those without, at 18% versus 0%, and eight partial responses versus none.
In addition, twice as many patients with MET-driven PRCC achieved stable disease than did those with MET-independent PRCC, at 50% versus 24%, while 61% and 20%, respectively, experienced some tumor shrinkage.
Disease progression occurred in 33 (75%) patients with MET-driven PRCC and 44 (96%) with MET-independent PRCC. The corresponding median progression-free survival (PFS) times were 6.2 and 1.4 months, respectively, a difference that was statistically significant and gave a hazard ratio of 0.33 in favor of MET-driven PRCC.
Choueiri and co-authors also note that “MET status was more predictive of response to savolitinib […] than a classification based on pathology.”
“This suggests that genomic profiling can better identify patients who may respond to savolitinib than can the type 1 or type 2 histologic subtype, adding relevance to the use of genomic profiling in such studies,” they write.
In terms of safety, the majority (88%) of patients experienced at least one treatment-related adverse event (AE), most commonly nausea, fatigue, vomiting, and peripheral edema.
There were three cases of serious treatment-related AEs: one instance each of grade 3 pneumonitis, grade 4 elevated transaminases, and grade 4 drug-induced liver injury, where the latter resulted in death from hepatic encephalopathy.
Choueiri et al conclude that their findings suggest that “savolitinib may suppress MET-driven tumor growth.”
They add: “Continued long-term follow-up will allow further assessment of the difference in PFS and provide data on overall survival.”
By Laura Cowen
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