Radical metastasectomy followed by observation is a commonly used strategy in selected patients with metastatic renal cell carcinoma ( mRCC ).
RESORT was the largest prospective study that assessed the role of angiogenesis inhibition in mRCC patients after radical metastasectomy.
The main eligibility criteria were a previous nephrectomy, predominant clear cell histology, a radical excision of no more than 3 metastases.
All patients were randomized ( 1:1 ) within 12 weeks from surgery to receive Sorafenib ( Nexavar ) or observation for a maximum of 52 weeks 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.
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.
From November 2012 to November 2017, 76 patients were enrolled ( 32 in Sorafenib and 36 in observation arm ); 6 patients were screening failure and 2 patients never started treatment.
An interim analysis was performed in the intention-to-treat population ( median follow-up 21 months ) included 68 patients with well balanced baseline characteristics between the two arms.
Median recurrence-free survival ( RFS ) was 29 months ( 95%CI 10-NA ) in Sorafenib arm versus 35 months ( 95% 17-NA ) in the observation arm: 12 and 24 months RFS was 62% ( 95% CI 46-84 ) and 52% ( 95% CI 35-76 ) in Sorafenib while 74% ( 95% CI 59-91 ) and 59% ( 95% CI 42-82 ) in observation arm respectively.
No differences in RFS were observed considering the stratification factors.
Grade 3 adverse events with Sorafenib were 22% vs 3% in the observation arm. Only 2 patients received the full Sorafenib dose, the remaining 30 patients had at least one interruption or dose reduction.
Considering the % 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.
In conclusion, Sorafenib was safe but did not affect recurrence-free survival in patients with metastatic renal cell carcinoma after complete metastasectomy. ( Xagena )
Source: Procopio G et al, ASCO ( American Society of Clinical Oncology ), 2018