SORCE rules out adjuvant sorafenib for RCC
medwireNews: Sorafenib should not be used in the adjuvant setting in patients with resected renal cell carcinoma (RCC) at intermediate or high risk of relapse, says the SORCE research team.
There was no significant improvement in either disease-free survival (DFS) or overall survival (OS) with either 1 or 3 years of treatment with the multitargeted tyrosine kinase inhibitor versus placebo, presenting author Tim Eisen, from the University of Cambridge in the UK, told the audience at the ESMO Congress 2019 in Barcelona, Spain.
He continued: “We therefore believe that active surveillance remains the global standard of care for patients in this risk group, and it is the appropriate control for current international adjuvant studies.”
The phase III trial included 1711 surgically treated RCC patients who had an intermediate or high risk of recurrence as per the Leibovich score; they were randomly assigned to receive adjuvant sorafenib for 3 years or for 1 year followed by placebo for 2 years, or placebo for 3 years. Initially the starting dose for sorafenib was 400 mg twice daily, but this was modified to a once-daily dose of 400 mg for the first 3 weeks, with escalation to the full dose for patients who could tolerate it.
The DFS rate at 5 years was 65% in the 3-year sorafenib arm and 67% in the placebo arm, with 10-year rates of 53% and 54%, respectively. As the proportional hazards assumption was violated, the investigators also reported the restricted mean survival time (RMST), which was again similar for the two groups, at a respective 6.81 and 6.82 years.
The results were similar for the comparison of 1 year of sorafenib treatment with placebo; the 5-year DFS rate was identical, at 67%, while the 10-year rates were 55% and 54%, respectively, and the RMST was 6.98 versus 6.79 years.
OS was also not significantly improved with either 3 years or a year of treatment with sorafenib relative to placebo, with 10-year rates of 70%, 69%, and 69%, respectively.
Eisen highlighted that “this was a difficult treatment to deliver, both because it was a long follow-up period for patients who we hoped had been cured […] and also because of the toxicities of sorafenib in this particular group of patients.”
Only a quarter of patients in the 3-year sorafenib group and a third of those in the 1-year sorafenib group completed treatment as per protocol. And indeed even in the placebo group, just over half of participants completed treatment.
The most common reason for discontinuation in the 3- and 1-year sorafenib groups was excessive toxicity, cited by 33.5% and 29.9% of patients, respectively.
The presenter expressed surprise not at the type of adverse events but at the severity of these events; for instance, grade 3 hand–foot skin reaction occurred in 24% of participants each in the 3- and 1-year sorafenib treatment arms.
He concluded that SORCE is “a definitive study” showing that “sorafenib should definitely not be used as adjuvant therapy” in this patient population.
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ESMO Congress 2019; Barcelona, Spain: 27 September–1 October