Vatalanib (V) for patients with previously untreated advanced malignant mesothelioma (MM): A phase II study by the Cancer and Leukemia Group B (CALGB 30107)

Abstract

7081 Background: Targeting both vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) may be an appropriate therapeutic strategy in MM. MM express VEGF, PDGF, and their receptors, suggesting autocrine growth-stimulating loops. VEGF inhibitors and PDGF inhibitors have in vitro activity in MM. In MM patients (pts), high VEGF levels correlate with poor outcome. Vatalanib inhibits VEGF and PDGF receptor tyrosine kinases. Methods: We conducted a phase II trial of V in pts with unresectable, histologically-confirmed MM, measurable disease, no prior therapy, ECOG performance status (PS) 0–1. Primary endpoint: 3-month (mo) progression-free survival (PFS). V 1250 mg, was given orally daily. CT scans were obtained Q6 weeks. Baseline serum VEGF, PDGF were determined. Results: 47 eligible pts (46 evaluable) enrolled at 19 sites from 7/03–11/04. Pt characteristics: male 92%, median age 75 (range 51–92; 64% were >70). Histology: epithelial 80%, sarcomatoid 11%, biphasic 9%. Site of origin: pleura 87%, peritoneum 6%, other 6%. PS 0/1: 21%/ 79%. 261 cycles were administered, median 3, range 1–32; 2 pts continue treatment. Grade 3/4 toxicities: neutropenia 2%, lymphopenia 2%, nausea/vomiting 15%/9%, increased ALT/AST 9%/6%, hypertension 2%, gastrointestinal bleed 2%. Partial response: 11% (5 pts), stable disease 66%. 3-mo PFS: 55% (95% CI: 40%, 68%), median PFS: 4.1 mo; median survival 10.0 mo. Median baseline serum levels in 40 pts: VEGF 425 pg/mL, PDGF 22754 pg/mL. There was no correlation between baseline VEGF or PDGF levels and response, PFS, or survival. Conclusions: The study did not achieve the protocol-specified 3-mo PFS of 75%. However, the objective response rate of 11% and median survival of 10 months are similar to other active single-agents for MM, which suggests that V may warrant further study in this disease. [Table: see text]