(CHICAGO, IL) — Eleven additional months of safety data collected after the final cut-off for analysis of progression-free survival (PFS) has confirmed the overall safety profile observed in patients with platinum-sensitive recurrent ovarian cancer in the randomized phase 3 OCEANS trial, according to a study reported during the 2012 American Society of Clinical Oncology Annual Meeting.
According to lead study author Carol Aghajanian, MD, of Memorial Sloan-Kettering Cancer Center, New York, the study met its primary endpoint of a statistically significant and clinically meaningful hazard ratio for PFS of 0.484. The double-blind multi-center trial randomized patients to gemcitabine 1000mg/m2 Days 1 and 8 and carboplatin AUC 4, Day 1 with concurrent placebo, followed by placebo (n=233) or gemcitabine/carboplatin plus concurrent bevacizumab 15mg/kg every 21 days, followed by bevacizumab (n=247). Secondary end points included objective response rate, overall survival, and safety.
Incidence of any grade adverse event (AE) was 100% in both arms; serious AEs occurred in 25.3% of patients in the placebo arm and 35.6% in the bevacizumab arm. Compared with placebo, patients in the bevacizumab arm had higher rates of grade 3 or higher proteinuria (9.7% vs. 0.9%), hypertension (17.8% vs. 0.4%), reversible posterior leukoencephalopathy syndrome (all grades; 0.8% vs 0%), thrombocytopenia (40% vs. 34%), and epistaxis (4.9% vs 0.4%), she reported. Grade 3 or higher non-CNS bleeding occurred in 5.7% of patients in the bevacizumab arm and 0.9% in the placebo arm.
More patients in the bevacizumab arm (20.6%) than in the placebo arm (4.7%) experienced an AE that led to discontinuation of study drug. In the bevacizumab arm, this was most commonly due to hypertension (4%), proteinuria (2.8%), epistaxis (1.2%), thrombocytopenia (1.6%), and reversible posterior leukoencephalopathy syndrome (0.8%).
Median number of cycles of bevacizumab in patients with grade 3 or higher proteinuria was 22.5; this AE resolved in 91.7% of patients. Among patients with grade 3 or higher hypertension, median number of cycles of bevacizumab was 16.5, and the AE resolved in 72.7%.
“The overall safety profile was similar to that seen at the time of the final PFS analysis,” Dr. Aghajanian said. “Higher incidences of proteinuria and hypertension were possibly related to longer bevacizumab treatment duration and resolved in the majority of patients.”