In the phase III SORCE trial reported in the Journal of Clinical Oncology, Eisen et al found no benefit of sorafenib vs placebo as adjuvant therapy in patients with renal cell carcinoma at intermediate or high risk of disease recurrence.

Study Details

The double-blind trial included 1,711 patients from six European countries and Australia undergoing excision of primary renal cell carcinoma. Patients were randomly assigned 2:3:3 between July 2007 and April 2013 to receive placebo for 3 years (n = 430), sorafenib for 1 year followed by placebo for 2 years (n = 642), or sorafenib for 3 years (n = 639). The initial sorafenib dose of 400 mg twice daily (received by 13% of patients in the sorafenib groups) was amended to 400 mg daily during the trial.

Overall, 84% of patients had clear cell histology; risk of recurrence was intermediate in 53% of patients and high in 47%. The primary outcome analysis was investigator-reported disease-free survival comparing 3 years of sorafenib vs placebo in the intent-to-treat population. 

Disease-Free Survival

Median follow-up at the time of analysis was 6.5 years. Despite permitted treatment adaptations including dose modifications, more than half of patients in the sorafenib groups stopped treatment by 12 months (median duration = 10.6 months with 3 years; and 11.7 months with 1 year of sorafenib vs 35.4 months with placebo).

No difference in disease-free survival was observed for the 3-year sorafenib group vs the placebo group, with 245 vs 167 events being observed (hazard ratio = 1.01, 95% confidence interval [CI] = 0.83–1.23; P = .95). Median disease-free survival was not reached in either group.

Since nonproportional hazards were observed (P = .042), a restricted mean survival time analysis was performed; estimated restricted mean survival time over 10 years was 6.81 years in the 3-year sorafenib group vs 6.82 years in the placebo group (difference = 0.01 year; P = .988). No difference in disease-free survival was observed between the 1-year sorafenib group vs the placebo group (HR = 0.94, 95% CI = 0.77–1.14; P = .509).

No differences in overall survival were observed when compared to the placebo group for the 3-year sorafenib group (HR = 1.06, 95% CI = 0.82–1.38; P = .638) or for the 1-year sorafenib group (HR = 0.92, 95% CI = 0.71–1.20; P = .541). Overall survival at 10 years was 70% in the 3-year group, 69% in the 1-year group, and 69% in the placebo group.  

In preplanned subgroup analyses, no significant differences for the 3-year or 1-year sorafenib groups vs the placebo group were observed among patients at high risk of recurrence or among those with clear cell renal cell carcinoma.

Adverse Events

Grade ≥ 3 adverse events occurred in 63.9% of patients in the 3-year sorafenib group, 58.6% of the 1-year sorafenib group, and 29.2% of the placebo group. Serious adverse events occurred in 24%, 21.6%, and 19.1% of patients, respectively. Grade 3 hand-foot skin reaction was reported in 24% of patients in each sorafenib group. Grade 3 hypertension occurred in 26% and 24% of the sorafenib groups and 20% of the placebo group.

The investigators concluded, “Sorafenib should not be used as adjuvant therapy for renal cell carcinoma. Active surveillance remains the standard of care for patients at intermediate or high risk of recurrence after nephrectomy and is the appropriate control of our current international adjuvant renal cell carcinoma trial, RAMPART [NCT03288532].”

Tim Eisen, MB BChir, PhD, of the Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Cancer Research UK, an educational research grant from Bayer, and others. For full disclosures of the study authors, visit ascopubs.org.