Pazopanib (GW786034) is active in women with advanced epithelial ovarian, fallopian tube and peritoneal cancers: Initial results of a phase II study

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5561 Background: Pazopanib 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 blocks tumor growth & inhibits angiogenesis. Clinical studies have demonstrated activity of anti-angiogenesis agents in ovarian carcinoma. Methods: Pts with epithelial ovarian, fallopian tube or primary peritoneal carcinoma; ECOG PS 0–1 with complete CA-125 response to initial platinum-based chemotherapy with subsequent rise to = 42 U/mL; no disease on CT; or non-bulky disease (masses ≤ 4 cm) were eligible. All pts must have received 1–2 prior regimens. Treatment consisted of pazopanib 800mg QD until PD, withdrawal due to AEs, or withdrawal of consent. Two-stage Green-Dahlberg design was employed requiring 2 CA-125 responses in Stage I (20 pts) to proceed to Stage II (15 pts). Primary endpoint was CA-125 response (= 50% decrease from 2 baseline samples, confirmed ≥ 21 d after initial response sample). Results: Data were available from 15/17 pts enrolled. Median age was 60 yrs (46–79). Majority of pts had platinum-sensitive disease to first line therapy (74%) and had 1 prior line of therapy (60%). 40% of pts relapsed < 6 mos, 27% relapsed 6–12 mos; 27% relapsed > 12 mos. CA-125 responses were seen in 7 pts (47%) with a median time to response of 29 d (5 pts have continuing response of 56–140 d and 2 pts had response duration of 56 & 112 d). SD was observed in 4 pts (27%) and PD in 4 pts (27%). Most common AEs were fatigue, diarrhea, nausea, vomiting, and headache. Most common Gr 3/4 AEs were diarrhea (n=2) and ALT elevation (n=2). Five pts (33%) withdrew due to an AE; 1pt (7%) withdrew due to a potentially disease-related AE (Gr 3 ascites) and 4 pts (26%) withdrew due to toxicity (Gr 3 fatigue, Gr 2 vomiting, Gr 3 double vision, Gr 3 AST/ALT elevations). Conclusions: Preliminary review of Stage I suggests that pazopanib monotherapy demonstrates biologic activity in pts with ovarian cancer with biochemical relapse following prior platinum chemotherapy. The study has met the response criteria to proceed to stage II of enrollment. No significant financial relationships to disclose.