For renal cell carcinoma, the results of ASSURE and S-TRAC were recently published. ASSURE showed no differences between sunitinib, sorafenib, or placebo in either DFS or OS. The lack of difference remained in the pre-planned subset analysis of patients with clear cell histology. S-TRAC, however, did find a difference in DFS between sunitinib and placebo, although there was no difference in OS. The ARISER which randomized patients 1:1 to girentuximab versus placebo showed no differences in DFS and OS.
Reports are expected soon from ATLAS which randomized patients 1:1 to adjuvant axitinib versus placebo. Similarly, EVEREST randomized patients 1:1 to adjuvant everolimus versus placebo and preliminary results are forthcoming. The SORCE trial has a unique randomization strategy consisting of 3:3:2 allocation to sorafenib for 3 years, sorafenib for 1 year, or placebo. The PROTECT trial randomizes patients 1:1 to pazopanib versus placebo. Publically available evidence suggests that this may be a negative trial, however, official results have not yet been reported.
The current adjuvant landscape trials vary by primary endpoints (DFS vs. OS vs. both), median DFS, median follow-up, histologies allowed (clear cell versus others), recurrence risk (different stage tumors allowed), adjuvant therapies, number of patients in the trial, planned duration of therapy, how dose reductions are applied, treatment discontinuation, imaging review/frequency, and study location. All are important to consider when interpreting results from these trials.
Currently planned trials are IMmotion which allocates patients 1:1 to atezolizumab versus placebo. The primary endpoint is DFS. PROSPER is another recently planned study that randomizes patients to neoadjuvant nivolumab followed by surgery followed by adjuvant therapy versus surgery followed by observation. Other adjuvant trials opening soon include a pemborlizumab-based trial and an nivolumab + ipilipumab combination. These studies should help to validate prognostic models, refine post-operative surveillance strategy, compare treatment effects after therapy discontinuation, and understand secondary treatment patterns.
Dr. Karam closed with the following take-home messages. First, only one study (S-TRAC) has shown a clinical benefit (DFS) in the adjuvant setting for RCC. Second, a deeper analysis of clinical and pathological materials from adjuvant trials. Third, preclinical models of adjuvant therapy are needed. Finally, he concluded by noting that it is an exciting time for adjuvant trials in kidney cancer.
Presenter: Jose A. Karam, MD, FACS, The University of Texas MD Anderson Cancer Center
Written By: Benjamin T. Ristau, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center
at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA