Table 2.
Differences in clinicopathologic variables and outcomes between the ASSURE and S-TRAC trials.
| ASSURE | S-TRAC | Comment | |
|---|---|---|---|
| Sponsors | ECOG | Pfizer | - |
| Risk criteria & tumor stage | UISS intermediate-high risk pT1b–4, NX, M0, G1–3 pTany, N1–2, M0 Only grades 3–4 included Only ECOG 0 or 1 included |
UISS intermediate-high risk pT3, NX, M0 pT4, NX, M0 pTany, N1–2, M0 All grades included All ECOG PS included |
ASSURE included lower risk patients, whereas S-TRAC included higher risk patients |
| Histology | Included non-clear-cell histology (~20%) | Clear-cell histology only | ASSURE included patients without clear-cell histology |
| Lymph nodes | Included N+ disease if fully resected | Included N+ disease if fully resected | - |
| Interventions | Sunitinib or sorafenib or placebo x 1 year | Sunitinib or placebo x 1 year | - |
| Dosing | Initially: sunitinib 50 mg/day, sorafenib 400 mg twice daily *Revised: sunitinib 25–37.5 mg/day, sorafenib 400 mg/day *After ~1,300 patients, increased as tolerated. |
*Sunitinib 50 mg/day *Allowed reductions only to 37.5 mg/day, depending on toxicity and severity. |
ASSURE expanded dose reduction to all patients and allowed sunitinib dosing as low as 25 mg/day |
| Dosing outcomes | *Treatment completion: sunitinib 56%, sorafenib 55%, placebo 89% *Among those patients starting at full dose |
Treatment completion: sunitinib 55%, placebo 69.4% Dosing reduction: sunitinib 45.8%, placebo 4.9% |
Mid-study starting dose reduction improved treatment completion and dosing reduction rates in ASSURE; however, the effective dose was reduced. |
| Randomized | N=1,943 Stratified by: histology (clear- cell vs. non-clear-cell), surgery (lap vs. open), ECOG (0 vs. 1), risk category (int. high vs. high vs. very high risk) |
N=615 Stratified by: UISS risk group, ECOG PS (<2 vs. ≥2), Country |
- |
| Outcomes | Primary: DFS Secondary: OS, DFS for clear-cell histology, toxic effects by NCI CTCAE v3.0 |
Primary: DFS Secondary: OS, safety/toxicity, patient reported outcomes, biomarker analysis |
- |
| Evaluation | Imaging: q4.5 months within first year, q6 months in second year, q12 months thereafter | Imaging: q3 months in years 1–3, q6 months in years 4–5, q12 months thereafter | More frequent imaging evaluation in S-TRAC |
| Centralized review | Only blinded investigator radiology review | Blinded centralized and investigator radiology review | Only central review, but not investigator review, was significant in S-TRAC |
| Median disease-free survival | Sunitinib 5.8, sorafenib 6.1, placebo 6.6 years (sunitinib vs placebo: HR 1.02, 95% CI 0.85–1.23, p=0.80; sorafenib vs placebo: HR 0.97, 95% CI 0.80–1.17, p=0.72). | Sunitinib 6.8, placebo 5.6 years (HR 0.76, 95% CI 0.59–0.98, p=0.03) | ASSURE: negative study; S-TRAC: positive study |
| Overall survival | No difference between groups *Median OS not reached for any group. |
Not mature at publication | - |
| Adverse events | ≥Grade 3 events: sunitinib 63%, sorafenib 70%, placebo 24% | ≥Grade 3 events: sunitinib 60.5%, placebo 19.4% | Similar between studies |
| Accrual | 2006–2010 United States and Canada |
2007–2011 Multi-national (21 countries) |
Potentially more generalizable results from S- TRAC |