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S-TRAC and Its Implications: Finally, a New Paradigm for Adjuvant Therapy Emerges ne of the more elusive goals in the treatment of renal cell carcinoma is now within reach based on results from a landmark trial in adjuvant therapy following nephrectomy in locoregional disease. And yet, much investigative work still needs to be done to achieve a long awaited improvement in overall survival. Two clinical trials, each with similar objectives yet producing distinctly different outcomes, highlight significant variations in disease-free survival with the use of adjuvant sunitinib. These trials help delineate important factors that may underlie the results following this strategy. Rarely can the results of a trial legitimately be considered a milestone, but the S-TRAC (Sunitinib as Adjuvant Treatment for Patients at High Risk of Recurrence of Renal Cell Carcinoma ) qualifies as a landmark study. With results from the S-TRAC trial reported by Ravaud et al, it was clear that a new era might be emerging in renal cell carcinoma (RCC) where previously we thought there was no hope—that of the benefit of adjuvant therapy.1 The S-TRAC trial represented the first “The S-TRAC trial represented the first positive study after many failed adjuvant trials for patients with RCC post nephrectomy. Although this positive trial yielded a cautionary acceptance for sunitinib in clear cell carcinoma only in a homogenously higher-risk patient population, it represents the beginning of a new optimism for adjuvant therapy benefits in kidney cancer.” positive study after many failed adjuvant trials for patients with RCC post nephrectomy. Although this positive trial yielded a cautionary acceptance for sunitinib in clear cell carcinoma only in a homogenously higher-risk patient population, it represents the beginning of a new 134 Kidney Cancer Journal optimism for adjuvant therapy benefits in kidney cancer. S-TRAC is also significant in at least one other respect: its results stand out compared to a similarly designed trial—ASSURE (Adjuvant Sunitinib or Sorafenib for High- Risk, Non-Metastatic Renal Cell Carcinoma) or ECOG 2805.2 In this phase 3 trial, involving patients with locally advanced RCC, investigators did not find any treatment advantage for adjuvant therapy with sunitinib or sorafenib over placebo. The most important question arising from a comparison of ASSURE vs STRAC is why did patients in S-TRAC respond to the sunitinib regimen while in the ASSURE trial they did not. A comparison of the two trials reveals how differing methodologies, including dosing strategies and patient selection had an impact on the results. Regardless of these differences, the focus needs to be on STRAC and how it can reshape the treatment landscape in locoregional RCC. Still a second key question is whether the FDA will approve sunitinib for this indication, thereby offering clinicians a remarkable new option in therapy. Sunitinib provides this exciting option, given the increase in disease-free survival and the manageable safety profile seen in S-TRAC. The results of this trial could change practice patterns because there is currently no standard treatment in this setting.1 Inside S-TRAC and Its Methodology In this trial, sunitinib was started at a full dose 50 mg for 4 weeks on, 2 weeks off, and was associated with a median duration of disease-free survival of 6.8 years (95% CI, 5.8–NR) in the sunitinib group vs 5.6 years (95% CI, 3.8–6.6) in the placebo group. The hazard ratio was 0.76 (P = .03). At 3 years, 64.9% of the sunitinib group was dis- Alexandra Drakaki, MD, PhD Assistant Professor of Medicine (Hematolgy/Oncology) and Urology UCLA Institute of Urologic Oncology Los Angeles, California Allan Pantuck, MD, FACS Professor of Urology UCLA Institute of Urologic Oncology Los Angeles, California O Keywords: Adjuvant therapy, S-TRAC, ASSURE, post nephrectomy, sunitinib, disease-free survival, locoregional RCC. Address for reprints and correspondence: Allan Pantuck, MD, 220 Medical Plaza Driveway, Los Angeles, CA 90024. Email: APantuck@mednet.ucla.edu


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