CHICAGO—Sunitinib was not found to be effective in improving overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC) compared with sorafenib, reported Ann-Lii Cheng, MD, National Taiwan University Hospital, Taipei, Taiwan, and colleagues at the American Society of Clinical Oncology’s 2011 Annual Meeting. However, progression-free survival (PFS) and time to progression (TTP) were similar for sunitinib and sorafenib. Dr. Cheng is part of the SUN1170 HCC Study Group.

This open-label trial compared the efficacy and safety of sunitinib with that of sorafenib and based on data from the sorafenib SHARP trial, which had a median overall survival (OS) of 10.7 months. The primary endpoint was overall survival and 600 patients/arm were required in this superiority/non-inferiority, Phase 3, international, randomized, multicenter, open-label trial. Secondary endpoints were PFS, TTP and safety.

Patients received either sunitinib 37.5mg/day or sorafenib 400mg twice daily. . Baseline characteristics for sunitinib/sorafenib, respectively was median age 59/59 years; Asian 76/75%; male 82/84%; ECOG PS 1 47/47%; hepatitis B/C infection (HBV/HCV) 55%/21% vs. 53%/22%; >3 courses of prior transcatheter arterial chemoembolization (TACE) 15/17%; vascular tumor invasion and/or extrahepatic spread 79/76%; ≥1 dose interruption 69/56% and ≥1 dose reduction 48/69%.

The study was stopped after a planned safety review by an Independent Data Monitoring Committee after 457 deaths had occurred; a higher incidence of serious adverse events (AEs) with sunitinib resulted in an unfavorable risk-benefit relationship vs. sorafenib. Enrollment was halted after 1,074 patients had been randomized from July 2008-May 2010. Sunitinib discontinuation was recommended, Dr. Cheng, said, and treatment changed to standard of care. Patients were notified and sunitinib discontinuation was recommended with the option for investigator discretion to continue therapy in cases of clinical benefit.

Median OS was 7.9  months for sunitinib and 10.2  months for sorafenib (HR 1.30 [1.13–1.50], P=0.0010); PFS was 3.6 and 3.0  months, respectively (HR 1.13 [0.99–1.30], P=0.1215) and TTP was 4.1 and 3.8  months, respectively (HR  1.13 [0.98–1.31], P=0.1688). Exploratory analyses for patients with HBV (sunitinib/sorafenib) found a median OS of 7.6/8.0 months (HR 1.10 [0.92–1.33], P=0.1714) and HCV, median 9.2 vs. 17.6 months (HR 1.52 [1.09–2.13],  The best objective response rate (ORR) was 2 complete responses and 33 partial responses in the sunitinib group and one complete response and 32 partial responses in the sorafenib group.

In the patients evaluable for safety (sunitinib n=526; sorafenib n=541), the most common Grade 3/4 adverse events were thrombocytopenia (30%) and neutropenia (25%) for sunitinib, and skin disorders (22%) for sorafenib. Any bleeding occurred in 49$% of the patients in the sunitinib arm and 25% of the sorafenib arm. Of the toxicity deaths on study, 18% occurred in the sunitinib group and 2% in the sorafenib group; these included dehydration with and without organ failure and CNS hemorrhage in the sunitinib group and esophageal varices/GI hemorrhage (3% for sunitinib vs. 1% for sorafenib).

Dr. Cheng and colleagues concluded that sunitinib did not demonstrate superiority or noninferiority in OS compared with sorafenib in patients with advanced HCC; however, PFS, TTP, and ORR were comparable between treatment arms. The frequency and severity of AEs were higher with sunitinib than sorafenib. In patients with HCV infection, OS was shorter with sunitinib.