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3558 Background: Aflibercept (AF) is a recombinant fusion protein that is a potent inhibitor of vascular endothelial growth factor (VEGF). This study was designed to assess the safety/tolerability, dose-limiting toxicities (DLTs), recommended Phase II dose, and PK of AF plus Gem. Methods: This combination trial explored escalating iv doses of AF, administered every 2 weeks(q2w), followed by standard weekly iv Gem (7w on/1w off, then 3w on/1w off every 4w). Results: 32 pts (M/F 9/23, median age 58 38–75, ECOG-PS 0/1/2: 10/21/1) were enrolled in 2 AF dose levels: 4.0 (n = 20) and 6.0 (n = 12) mg/kg. Primary tumors included pancreas (11), breast (7), sarcoma (3), and others (11). Most (9/11) pancreatic pts were first-line. Other pts were heavily pre-treated, with a median of 31–11 prior lines. Pts received a median of 2 1–9 4w treatment cycles (cy). During the dose escalation phase, no AF-related DLT (first 4w cy) was observed. Gr > 3 NCI-CTCAE toxicities observed across doses included: neutropenia (34%), thrombocytopenia (22%), hypertension (HTN) (22%), proteinuria (PrU) (6%), pulmonary embolus (6%, including one Gr 5 at 4 mg/kg in a pancreatic cancer pt), and unstable angina, hemorrhage, blurred vision (3% each). In 4/12 pts (33%) at 6 mg/kg, Gr 3 HTN not controlled despite 4w treatment and/or Gr 3 PrU contributed to early treatment discontinuation. One partial response was noted (breast at 4mg/kg) and 10 pts had stable disease. Free and bound AF concentrations with Gem are comparable to those observed with AF alone. At both doses, free AF exceeds bound AF over dosing interval, suggesting sustained effective trapping of VEGF. Conclusions: AF 4 mg/kg q2w combined with weekly gemcitabine was selected for further investigations. Updated data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis
Patnaik et al. (Tue,) studied this question.