Neither sunitinib nor sorafenib reduced disease recurrence in patients with locally advanced renal cell carcinoma (RCC) when these agents were given to patients as adjuvant therapy, according to the results of a new study.
Neither sunitinib nor sorafenib reduced disease recurrence in patients with locally advanced renal cell carcinoma (RCC) when these agents were given to patients as adjuvant therapy, according to the results of a new study. These results were presented at a press conference in advance at the 2015 ASCO Genitourinary Cancers Symposium.
The ASSURE (Eastern Oncology Cooperative Group E2805) study showed that both sunitinib and sorafenib adjuvant therapy resulted in an average disease recurrence time of 5.6 years compared to 5.7 years in the placebo arm.
“[This is] a very important study, the first adjuvant study using tyrosine kinase inhibitors in kidney cancer,” said Charles Ryan, MD, leader of the genitourinary medical oncology program at the University of California San Francisco, and press conference moderator. “The fact that it is a negative study does not diminish its importance. [Tyrosine kinase inhibitors] are not chemotherapy and act in a different manner; therefore, they may not be as effective against micro-metastatic disease as chemotherapy in other tumors.”
“It was not intuitive that adjuvant use would be beneficial, and that underscores the importance of this study,” added Ryan.
According to presenter and study author Naomi B. Haas, MD, Associate Professor of Medicine at the Abramson Cancer Center of the University of Pennsylvania in Philadelphia, the authors are currently analyzing patient samples to understand whether a subset of patients may benefit from either of these oral tyrosine kinase inhibitors against vascular endothelial growth factor receptors (VEGFR) and platelet-derived growth factor receptors (PDGFR).
This is the first study to test whether VEGF inhibitors can decrease the risk of recurrence for these locally advanced RCC patients. Approximately one-third of these patients develop metastatic disease. VEGF-targeted tyrosine kinases have resulted in some benefit in the metastatic RCC setting. Currently, there is no standard of care adjuvant therapy. Most patients are closely observed for disease progression.
A total of 1,943 patients were randomized to receive daily sunitinib, twice daily sorafenib, or placebo for 12 months. All patients were high-risk for recurrence based on tumor size and grade, and lymph node status.
There were no differences in the 5-year disease-free survival rates between the experimental arm and the placebo arm, 53.8%, 52.8%, and 55.8%, for the sunitinib, sorafenib, and placebo arms, respectively.
Likewise, there were no differences between either experimental arm or the placebo arm. The 5-year overall survival rate was 76.9%, 80.7%, and 78.7% in the sunitinib, sorafenib, and placebo arms, respectively.
There were higher incidences of hypertension in the two treatment arms compared to the placebo group. Grade 3 or higher hypertension was experienced by 16% in each of the experimental arms and in 4% of the placebo arm. Grade 3 or higher hand-foot reaction was experienced by 15%, 33%, and 1% of patients in the sunitinib, sorafenib, and placebo arms, respectively.
The side effects included hand-foot syndrome, diarrhea, and hypertension, said Haas. Hematologic effects included thrombocytopenia in 1% of patients in the sunitnib arm, less than 1% in the sorafenib arm and in no patients in the placebo arm.
Adjuvant treatment of locally advanced kidney cancer is an area of continuing research. Several trials using other VEGF inhibitors have finished accruing patients and are awaiting analysis. Trials using immunotherapy and other targeted therapy approaches are being planned as well.