Sorafenib and Sunitinib May Cause More Harm Than Good in Patients With RCC

Two inhibitors of the vascular endothelial growth factor receptor (VEGFR), approved by the FDA in the treatment of metastatic renal cell cancer (RCC), do not prevent cancer recurrence when used in the adjuvant setting following surgery, a new study by researchers at the Abramson Cancer Center has confirmed.

A year back, the authors presented preliminary results of their study at the 2015 Genitourinary Cancer Symposium. They showed that the average period to disease recurrence was similar between those who received the 2 angiogenesis inhibitors (sorafenib or sunitinib) after surgery (5.6 years) and those treated with placebo (5.7 years). The 2 VEGFR inhibitors were evaluated in 1943 patients with RCC who were a part of a double-blind, placebo-controlled, multi-institutional phase 3 study that included 226 centers in the USA and Canada. Patients were randomly assigned 1:1:1 to receive sunitinib, sorafenib, or placebo following stratification based on recurrence risk, histology, Eastern Cooperative Oncology Group (ECOG) performance status, and surgical approach. The treatment followed surgical removal of the patients’ kidney tumors.

The researchers compared disease-free survival (DFS) between each experimental group and the placebo group and found no significant difference between DFS. Median DFS was 5.8 years for sunitinib (hazard ratio [HR], 1.02; 97.5% CI, 0.85-1.23; P =.8038)6.1 years for sorafenib (HR 0·97; 97·5% CI, 0·80—1·17, P =·7184), and 6.6 years for placebo.

Most common treatment-related toxicities of grade 3 or greater included hypertension, hand-foot syndrome, rash, and fatigue. Additionally, 5 deaths were reported that were related to the treatment or within a month of ending the treatment. High toxicity resulted in significant treatment discontinuation, the authors write, even after dose reduction. “These results provide a strong rationale against the use of these drugs for high-risk kidney cancer in the adjuvant setting and suggest that the biology of cancer recurrence might be independent of angiogenesis,” the authors conclude.

In an associated press release, the first author of the study, Naomi B. Haas, MD, said, “The current standard of care for these patients is close observation. Unfortunately, we found that the use of sunitinib or sorafenib in this setting did not reduce the incidence of recurrence as compared to placebo. Fortunately, the use of these drugs in this setting did not appear to make the outcome of patients receiving them any worse.”

The authors continue to evaluate blood and urine samples from trial participants to better understand responders to these drug in the adjuvant setting of kidney cancer. “This will afford opportunities to uncover molecular clues and other information that could help explain why some patients had a recurrence of their cancer or a spreading elsewhere and others did not,” Haas said.

Reference

Haas NB, Manola J, Uzzo RG, et al. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial [published online March 8, 2016]. Lancet. doi:http://dx.doi.org/10.1016/S0140-6736(16)00559-6.