Radical metastasectomy followed by sorafenib versus observation in patients with clear cell renal cell carcinoma: extended follow up of efficacy results from the randomized phase II RESORT trial.

Background: The RESORT trial showed no longer relapse free survival (RFS) with sorafenib following radical metastasectomy versus observation in metastatic renal cell carcinoma patients. We present the updated 42-month follow up data. Methods: The phase II RESORT trial randomized patients (1:1) to sorafenib or observation for 52 weeks within 12 weeks from surgery. RFS, the time from randomization to disease relapse or death, was the primary endpoint. Results: Sixty-nine patients were randomized between November 2012 and November 2017. We analyzed 68 patients (32 in sorafenib and 36 in observation arm). 81% in sorafenib arm and 80% in observation arm had one metastasis (lung was the main involved site). At a median follow-up of 42 months (interquartile range 31-58), in the observation arm the median RFS was 35 months, RFS probability was 57% (95% CI 42-76%) at 24 and 44% (95% CI 30-65%) at 48 months. In the sorafenib arm, median RFS was 21 months, RFS probability was 50% (95% CI 34-71%) at 24 and 32% (95% CI 18-57%) at 48 months (p=0.342;HR 1.35;95% CI 0.72-2.54). 47% and 37.5% of patients in the two arms, respectively, are disease free. Site of relapses was independent from the previous metastasectomy site. Conclusion: Sorafenib after metastasectomy did not improve RFS, but surgery in selected patients potentially improves survival. At a median follow-up of 42 months, 47% in the observation arm are relapse-free Clinical trial registration: www.clinicaltrials.gov identifier is NCT0144480.

Expert review of clinical pharmacology. 2021 Jan 20 [Epub ahead of print]

A Mennitto, E Verzoni, F Cognetti, R Miceli, M Milella, A Mosca, V E Chiuri, A Bearz, F Morelli, C Ortega, F Atzori, M Donini, M Claps, V Guadalupi, P Sepe, V Cappelletti, F G de Braud, G Procopio

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 Medicine, Medical Oncology, University and Hospital Trust of Verona , Verona, Italy., Multidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS , Candiolo, 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., Department of Medical Oncology, Ospedale S. Lazzaro ASL CN2 Alba-Bra , Cuneo, Italy., Medical Oncology Department, University Hospital, University of Cagliari , Cagliari, Italy., Medical Oncology Department, Ospedale di Cremona , Cremona, Italy., Biomarker Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale Tumori di Milano , Milan, Italy.