ASCO 2018: RESORT - A Randomized, Open Label, Multicenter Phase 2 Study, to Evaluate the Efficacy of Sorafenib in Patients with mRCC after a Radical Resection of the Metastases (original) (raw)

Chicago, IL (UroToday.com) Giuseppe Procopio, MD, from Milan, Italy provided results from the RESORT trial, a phase II trial evaluating the efficacy of sorafenib in patients with mRCC after resection of metastases. The integration between surgery and medical treatment for these patients is debated, as radical metastasectomy could play a role in selected cases. Currently, there is no evidence to support the use of medical therapy after a radical metastasectomy, and as such observation is a commonly used strategy. RESORT was the largest prospective study that assessed the role of angiogenesis inhibition with sorafenib among mRCC patients after radical metastasectomy.

Eligibility criteria for RESORT included:

• Previous nephrectomy
• Predominant clear cell histology
• A radical excision of no more than 3 metastases, with the absence of radiological residual lesions following surgical removal
• No more than three months from radical resection of metastases
• ECOG performance status 0-2 All patients were randomized (1:1) within 12 weeks from surgery to receive sorafenib or observation for a maximum of one year with stratification according to time from nephrectomy to metastases (more vs less than 12 months), site of disease (lung vs others) and number of lesions (single vs multiple). Sorafenib was administered at the standard dose 400 mg twice daily, and radiologic restaging was performed every 12 weeks. The primary endpoint was recurrence-free survival (RFS), defined as the time from randomization to disease relapse or death. Based on a sample size calculation for an RFS improvement of 12 months (observation) to 18 months (sorafenib), each arm required 66 patients.

The RESORT trial was designed in 2010, with the first person enrolling in November 2012. Through November 2017, 76 patients were enrolled: 32 in sorafenib and 36 in observation arm, including six patients that were screening failures and two patients that never started treatment. An interim analysis was performed in the intention to treat population at a median follow-up of 21 months (IQR 8-32 months; RFS follow-up cutoff April 17, 2018). In December 2017, an early termination of the trial was decided and thus the planned sample size was not reached. The reasons cited for early termination included (i) the long-time of accrual, and (ii) the availability of new and more active agents in the landscape of mRCC. Among 68 evaluable patients, there were well-balanced baseline characteristics between the two arms, with the most common sites of metastasis being the lungs and adrenal glands. The median RFS was 29 months (95%CI 10-NR) in sorafenib arm versus 35 months (95%CI 17-NR) in the observation arm. The 12 month RFS rate was 62% (95%CI 46-84) for sorafenib and 74% (95% CI 59-91) for observation, while the 24 month RFS rate was 52% (95%CI 35-76) for sorafenib and 59% (95%CI 42-82) in the observation arm. No differences in RFS were observed considering the stratification factors. Grade 3 adverse events with sorafenib were 22% vs 3% in the observation arm. Unfortunately, only two patients received the full sorafenib dose, while the remaining 30 patients had at least one interruption or dose reduction. Considering the percent of administered vs planned dose as a continuous variable in a Cox model, a slight decrease of the recurrence risk was observed when increasing sorafenib dose, however, the number of events observed was too small to obtain reliable estimates.

Procopio concluded with several statements:

• The RESORT trial did not meet its primary endpoint of improving RFS with sorafenib vs observation after radical metastasectomy
• The poor compliance/tolerability of patients to the full dose of sorafenib represented a major issue and may partially justify the negative results
• The data suggest that perhaps consideration should be given for a more homogenous population (ie. lung metastasectomy) for further investigations Clinical trial information: NCT01444807

Presented by: Giuseppe Procopio, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Co-Authors: Francesco Cognetti, Rosalba Miceli, Michele Milella, Alessandra Mosca, Vincenzo Emanuele Chiuri, Alessandra Bearz, Franco Morelli, Cinzia Ortega, Francesco Atzori, Maddalena Donini, Raffaele Ratta, Antonia Martinetti, Rosanna Montone, Filippo G. De Braud, Vera Cappelletti, Elena Verzoni; Oncologia Medica, Istituto Nazionale Tumori Regina Elena, Roma, Italy; Department of Medical Statistics, Biometry, and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Medical Oncology A, Regina Elena National Cancer Institute, Rome, Italy; Oncology, Maggiore Della Carita University Hospital, Novara, Italy; Ospedale Vito Fazzi, Lecce, Italy; National Cancer Institute, Aviano, Italy; IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; Azienda Sanitaria Locale CN2, Alba, Italy; Medical Oncology Department, University Hospital, University of Cagliari, Cagliari, Italy; SC Oncologia, Ospedale di Cremona, Cremona, Italy; Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA