In the Italian RESORT trial, sorafenib did not affect recurrence-free survival in patients with mRCC following radical resection of metastases.
Sorafenib appears to be safe but did not impact recurrence-free survival (RFS) in patients with metastatic renal cell carcinoma (mRCC) after complete radical resection of the metastases, according to Italian investigators of the randomized, open label, multicenter phase II RESORT trial. The study findings (abstract 4502) were reported at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.
Sorafenib is approved for the treatment of advanced RCC, advanced hepatocellular carcinoma, and radioactive iodine–resistant advanced thyroid carcinoma. Lead investigator of RESORT, Giuseppe Procopio, MD, head of the Genitourinary Unit at the Istituto Nazionale dei Tumori, Milan, Italy, and colleagues note that radical metastectomy followed by observation is a commonly used strategy in selected mRCC patients, so they assessed the clinical effect of sorafenib on outcomes in this patient population.
RESORT is the largest prospective study to assess the role of angiogenesis inhibition in mRCC patients after radical metastectomy. The main eligibility criteria included a previous nephrectomy, predominant clear cell histology, and a radical excision of no more than three metastases. Radiologic restaging was performed every 12 weeks. The primary endpoint for this study, RFS, was defined as the time from randomization to disease relapse or death. The investigators also collected blood samples for exploratory analysis at defined times.
From November 2012 through November 2017, a total of 76 patients were enrolled in the study (32 in the sorafenib arm and 36 in observation arm). Patients in the sorafenib arm received the standard dose, 400-mg twice daily. An interim analysis was performed in the intention-to-treat (ITT) population, with a median follow-up at 21 months that included 68 patients. Both arms were well balanced in terms of baseline characteristics.
Median RFS was 29 months in the sorafenib arm and 35 months in the observation arm. The proportion of patients with RFS was 62% at 12 months and 52% at 24 months in sorafenib arm; and was 74% at 12 months and 59% at 24 months in the observation arm. Grade 3 adverse events (AEs) occurred in 22% of patients in the sorafenib arm vs 3% in the observation arm. In addition, the study showed that only 2 patients received the full sorafenib dose, and the remaining 30 patients had at least one interruption or dose reduction.
The investigators commented, “Considering the [percentage] of administered vs planned dose as a continuous variable in a Cox model, a slight decrease of the recurrence risk was observed when increasing [the sorafenib dose], however the number of events observed was too small to obtain reliable estimates.”