Metastatic papillary renal cell carcinoma in the era of targeted therapy – a retrospective study from three European academic centres

Abstract

Background: Metastatic papillary renal cell carcinoma (mPRCC) is understudied. The disease is often aggressive and specific treatment options are lacking. Patients and methods: mPRCC patients (n ¼ 86) referred to three academic centres in Sweden and Germany in the years 2005-2015 were retrospectively identified from medical records. Statistical analyses included Kaplan-Meier curves and calculation of Cox proportional hazards, generating hazard ratios with 95% confidence intervals. The aim of the study was to evaluate overall survival (OS) of mPRCC patients treated outside of clinical trials in the era of targeted agents (TA) and to identify clinically useful prognostic factors. Results: Median OS of all mPRCC patients was 11.2 months. TA were used in 77% of the patients and associated with younger age and better Eastern Cooperative Oncology Group performance status (PS). Brain metastases were common (28%). Patients with synchronous or metachronous metastases had similar OS. Variables independently associated with risk of death included age !60 years, worse PS and !3 metastatic sites. The MSKCC criteria did not provide additional prognostic information. A subgroup analysis of TA-treated patients revealed an association of lymph node metastasis with risk of death in addition to the other prognostic factors. Conclusion: OS in mPRCC remained short in the era of targeted agents. Age, PS, and number of metastatic sites provided independent prognostic information.

Case of Hereditary Papillary Renal Cell Carcinoma Type I in a Patient With a Germline MET Mutation in Russia

“…The targeted MET inhibitor savolitinib led to a 4-fold increase in relapse-free survival in papillary RCC with MET mutation (20). Multikinase inhibitors (sunitinib, sorafenib, and axitinib) have been observed to induce more objective responses when used as targeted therapies to treat various non-clear cell RCCs, including papillary RCC, in the multicenter clinical study setting, and their combinations with MET or mTOR kinase inhibitors have been evaluated in clinical studies (21,22). MET inhibitors may be applicable in targeted therapy of HPRC; especially foretinib, which has been shown to be effective in papillary carcinomas of the kidney harboring germline MET mutations (23).…”