Author(s): Beth Karlan, Jianfeng Lu, Lynn Navale, Erik Rasmussen, YuNien Sun
Background: AMG 386, an investigational peptibody, inhibits tumor angiogenesis by preventing angiopoietins 1/2 and Tie2 receptor interaction. A phase II, double-blind, controlled study (NCT00479817) evaluated toxicity and efficacy of AMG 386 + paclitaxel (P) in recurrent ovarian cancer pts. Increased AMG 386 exposure in that study was associated with longer progression-free survival (PFS; Lu et al., JCO 2010; 28 [Suppl]: 5042). Here, these analyses were applied to pts electing OL AMG 386 monotherapy after progression in the placebo group. Methods: Pts with recurrent epithelial ovarian, fallopian tube, or peritoneal cancer (≤3 prior anticancer therapies, GOG ≤1) were randomized 1:1:1 to P IV QW (3 on/1 off) + AMG 386 (3 or 10 mg/kg) or placebo IV QW. In the placebo group, pts who progressed and stayed eligible could receive OL AMG 386 10 mg/kg IV QW monotherapy. In pts receiving AMG 386 monotherapy, post-hoc analyses evaluated PFS per RECIST, objective response rate (ORR), adverse events (AEs), and the relationships between high and low AMG 386 exposure (based on a median AUCSS of 10.6 mg*hr/mL) and efficacy (PFS per RECIST, ORR). Results: 161 pts were randomized. 18 pts received OL AMG 386 monotherapy (range: 1-56 infusions). At the time of analysis, PFS was 3.2 mo. ORR was 0%. 6 pts had stable disease (SD), 7 had progressive disease (PD). Common AEs were abdominal pain (n = 6), fatigue (n = 5), peripheral edema (n = 5), nausea (n = 5), urinary tract infection (n = 5), and vomiting (n = 5); grade ≥ 3 AEs in more than 1 pt were pleural effusion (n = 2; all grade 3), small intestinal obstruction (n = 2; all grade 3), and ovarian cancer (n = 2; all grade 5). PFS was longer in the high- (n = 9) vs low-exposure (n = 9) group (7.2 vs 1.8 mo; HR = .266, p = .041). Precrossover PFS was similar between high- and low-exposure groups (5.5 vs 4.5 mo; HR = 1.146, p = .812). For both groups, ORR was 0%. In the high-exposure group, 4 pts had SD, 3 had PD. In the low-exposure group, 2 pts had SD, 4 had PD. Conclusions: In line with results from a phase II study of AMG 386 + P, pts with recurrent ovarian cancer who received AMG 386 monotherapy and had high AMG 386 exposure had longer PFS than pts with low exposure. Toxicity was similar in both groups.