4008 Background: In a double-blind phase 3 trial, SU improved PFS vs PBO (11.4 vs 5.5 months; HR 0.418, 95% CI 0.263, 0.662; p=0.0001) and was well tolerated in pts with advanced well-differentiated, unresectable NET that had progressed in ≤12 months (NEJM, Feb 2011). Initial OS showed a benefit for SU over PBO, but median OS was not reached (NR). Here we report updated results of median OS and also PFS assessed by BICR to correct for potential unblinding due to identifiable adverse events (AE).
METHODS
Pts were randomized 1:1 to SU 37.5 mg as a continuous daily dose or PBO, each with best supportive care. Primary endpoint was PFS; secondary endpoint was OS. Median OS and HR were estimated using Kaplan-Meier (K-M) methods and Cox proportional hazards models. Baseline and on-study CT/MRI scans were evaluated by a 2-reader, 2-time point lock, followed by a sequential locked-read, batch-mode paradigm by blinded, third-party radiologists.
RESULTS
171 pts were randomized (SU, n=86; PBO, n=85) from 6/2007 to 4/2009. The trial ended early when an independent data monitoring committee noted efficacy favoring SU and more serious AEs and deaths with PBO. The study was unblinded at closure, and pts were offered open-label SU. At study end, there were 9 and 21 deaths in SU and PBO arms, respectively; HR of 0.409 (95% CI 0.187, 0.894; p=0.0204) favoring SU. By 6/2010, there were 34 and 39 deaths, respectively; median OS was 30.5 (95% CI 20.6, NR) and 24.4 (95% CI: 16.3, NR) months, respectively. The HR of 0.737 (95% CI 0.465, 1.168; p=0.1926) continued to favor SU; a K-M plot showed early/persistent separation of curves. For BICR analysis, scans were collected for 170 (99.4%) pts, with 160 (93.6%) having complete scan sets/time points. Median PFS by BICR was 12.6 vs 5.8 months for SU and PBO (HR 0.315 [95% CI 0.181, 0.546; p=0.000015]).
CONCLUSIONS
SU led to a 6.1-month improvement in median OS vs PBO, and BICR analysis confirmed the investigator-assessed PFS benefit of SU. These updated results support the robustness of the initial findings and the clinical benefit of treatment with sunitinib.