Effective adjuvant therapy for solid tumors is the holy grail of surgery. Adjuvant systemic therapies have remained elusive in urologic tumors, with none currently approved. Dozens of adjuvant renal cell carcinoma (RCC) clinical trials have been reported evaluating radiation, first-generation immunotherapies, and monoclonals alone or in combination. None have been clinically successful. Intense efforts have been undertaken to study targeted therapies in high risk, non-metastatic RCC after surgical resection. Two such trials recently reported include ECOG’s ASSURE (Adjuvant Sorafenib and Sunitinib for Unfavorable Renal Carcinoma) trial and Pfizer’s STRAC (Sunitinib Trial in Adjuvant Renal Cancer). ASSURE randomized 1943 patients (647 to sunitinib, 649 to sorafenib, 647 to placebo), while STRAC randomized 615 patients (306 to sunitinib, 309 to placebo). ASSURE reported no difference in disease-free survival (DFS) or overall survival (OS),[i] whereas STRAC reported improved DFS among centrally reviewed cases (HR=0.76) but no difference in OS.[ii] The difference in reported outcomes has sparked considerable discussion. Given conflicting results, how do we decide if we should recommend adjuvant therapy for high-risk fully resected RCC?
First, we need to define a framework of what constitutes healthcare “value” in oncology. The Institute of Medicine has identified 6 elements of value in cancer care: safety, effectiveness, efficiency, patient-centeredness, timeliness, and equity. Of these, the American Society of Clinical Oncology selected only 3 for its value framework; effectiveness, toxicity, and efficiency (cost).[iii] A thoughtful tool with which to assess these tradeoffs is the drug abacus (www.drugabacus.org), an online calculator allowing users to assign “value” in various domains such as incremental survival benefit and trade it off versus efficacy, novelty of mechanism, toxicity, cost of development, burden of disease, and other factors. It then compares your “value price” to the manufacturer’s price.
When high-level trials fail to produce a consistent and reproducible result, healthcare teams must contextualize the possible survival benefits in view of their risks and costs. Physicians and provider organizations must define and improve value because ultimately value is determined by how medicine is practiced.3 Adjuvant treatments for RCC are no exception.
Robert G. Uzzo, MD, FACS, is a Professor and Chairman of the Department of Surgery and the G. Willing “Wing” Pepper Chair in Cancer Research at Fox Chase Cancer Center at Temple University School of Medicine in Philadelphia.
- Haas NB, Manola J, Uzzo RG, et al Lancet 2016;387:2008-2016.
- Ravaud A, Motzer RJ, Pandha HS, et al N Engl J Med 2016; published online ahead of print Oct 9.
- Young RC. N Engl J Med 2015;373:2593-2595.