Sorafenib Versus Observation Following Radical Metastasectomy for Clear-cell Renal Cell Carcinoma: Results from the Phase 2 Randomized Open-label RESORT Study.

In selected metastatic renal cell carcinoma (mRCC) patients, radical metastasectomy followed by observation is a potential strategy. It is still to be defined whether systemic therapy should be administered following metastasectomy.

To assess the potential benefit of postoperative treatment with sorafenib compared with observation alone after radical metastasectomy in mRCC patients.

The RESORT trial was a multicenter, randomized, open-label, phase 2 study conducted between November 2012 and November 2017 in Italy. Patients with clear-cell mRCC pretreated with nephrectomy and undergoing radical metastasectomy (three or fewer lesions) were eligible for the study. Patients were randomized (1:1) within 12 wk from metastasectomy to sorafenib (standard dose 400 mg twice daily) or observation for a maximum of 52 wk. Stratification factors were interval from nephrectomy, site, and number of lesions. Overall, 76 patients were screened and 69 were randomized: 33 were assigned to sorafenib and 36 to observation. The primary endpoint was recurrence-free survival (RFS). Secondary endpoints were overall survival and the safety profile.

RFS curves were estimated with the Kaplan-Meier method, and the log-rank test was used to statistically compare the curves.

At a median follow-up of 38 mo, median RFS was 37 mo (95% confidence interval [CI] 20-not available [NA]) in the observation arm versus 21 mo (95% CI 11-NA) in the sorafenib arm (log-rank test p = 0.404), with 12-, 24-, and 36-mo RFS probability of 74% versus 63%, 59% versus 49%, and 50% versus 41%, respectively, in the observation versus the sorafenib arm. Any-grade adverse event (AE) rates were 84% in the sorafenib arm and 31% in the observation arm; grade ≥3 AE rates were 22% and 3% in the sorafenib and the observation arm, respectively, with a rate of treatment discontinuation for AEs of 19% in the sorafenib arm.

This prospective study showed that systemic treatment with sorafenib did not increase RFS as compared with observation in mRCC patients following radical metastasectomy.

This article reports the clinical outcome of patients with metastatic renal cell carcinoma treated with sorafenib or managed with an observation-alone strategy after the radical surgery of metastases. We found that sorafenib did not improve the patient outcome in terms of relapse-free survival in this selected population.

European urology oncology. 2019 Sep 18 [Epub ahead of print]

Giuseppe Procopio, Giulia Apollonio, Francesco Cognetti, Rosalba Miceli, Michele Milella, Alessandra Mosca, Vincenzo Emanuele Chiuri, Alessandra Bearz, Franco Morelli, Cinzia Ortega, Francesco Atzori, Maddalena Donini, Raffaele Ratta, Alessandra Raimondi, Melanie Claps, Antonia Martinetti, Umberto Capitanio, Filippo G de Braud, Vera Cappelletti, Elena Verzoni

Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: ., Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Medical Oncology Department, Istituto Nazionale Tumori Regina Elena, Rome, Italy., Department of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Department of Oncology, Maggiore Della Carità University Hospital, Novara, Italy., Medical Oncology Department, Ospedale Vito Fazzi, Lecce, Italy., Medical Oncology Department, National Cancer Institute, Aviano, Italy., Medical Oncology Department, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy., Medical Oncology Department, Istituto per la Ricerca e la Cura del Cancro di Candiolo, Torino, Italy., Medical Oncology Department, University Hospital, University of Cagliari, Cagliari, Italy., Medical Oncology Department, Ospedale di Cremona, Cremona, Italy., Division of Experimental Oncology, Urological Research Institute, San Raffaele Scientific Institute, Milan, Italy., Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.