A phase II study of pazopanib in recurrent or persistent ovarian (EOC), peritoneal (PPC), or Fallopian tube cancer (FTC): A Spanish Ovarian Cancer Group (GEICO) study.
5068 Background: Pazopanib (P) is a potent and selective multi-targeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-a/β, and c-kit that inhibits angiogenesis. Signaling blockade of these pathways is associated with anti-tumor and anti- angiogenesis activity. Methods: Eligible patients (pts) had persistent or recurrent EOC/PPC /FTC up to 2 prior cytotoxic regimens. They had to have received at least a platinum–based line and fulfill platinum resistant criteria. Treatment consisted of P 800 mg orally QD until disease progression or prohibitive toxicity. The primary endpoint was Clinical Benefit Rate (CBR) defined as Complete Response (CR) plus Partial Response (PR) plus Stable Disease (SD) ≥ 8 weeks by RECIST v1.1.An optimal two-stage Simon design was utilized with H1and H0set at 60%and 40% respectively; Power =90% significance level of 5% (Stage 1: = 25pts; total=66). Correlative studies to identify angiogenic biomarkers to predict response to P were performed. Results: From 12/10 to 7/11, 25 pts were enrolled, 21 pts had EOC, 2PPT, and 2FTC. Median age: 64 years (range 43-81), ECOG 0/1/2:12/11/2 pts. Prior chemotherapy regimens 1/2:10/15 pts. Median weeks on treatment: 8 (range 4-25). Most frequent adverse events (AEs) were asthenia (56%), hypertension (36%) and diarrhea, nausea and anorexia (20% each).Grade 3 toxicities: Hypertension (6pts), ALT/AST elevations (3 pts), asthenia (2 pts), DVT (1pt), Fistula (1 pt), Anemia (1 pt). Six pts required dose reduction to 600 mg due to toxicity.Reasons for stopping study treatment: PD (18pts), AEs (3pts) and investigator decision (2pts). First stage analysis showed: PR:1/25, SD: 9/25, CBR:10/25; 40% (95% CI 21.1%-61.3%).No correlation between GCIG CA-125 response and RECIST criteria was established, 8 versus 1 response respectively. Median PFS was 1.83 months (95% CI 1.67-2). Conclusions: The CBR observed at the first stage did not reach the planned statistical hypothesis (CBR:12 pts). Therefore, the lack of activity of P in platinum resistant EOC/PPT/FT led to discontinuation of the study. Translational study results will be presented in an additional abstract.