CALGB 30601: A phase II study of dasatinib (D) in patients (pts) with previously treated malignant mesothelioma (MM)

Abstract

BACKGROUND: SRC is commonly over-expressed in MM. D is a potent inhibitor of SRC family kinases, EphA2 and PDGFRβ. There are no approved therapies for MM pts who progress on pemetrexed. We therefore conducted a phase II trial of D in MM pts who had received 1 prior pemetrexed-based regimen. METHODS: Single arm phase II. Eligible pts had unresectable MM, PS 0-1, measurable disease, and no symptomatic effusions. Primary endpoint: Progression-free survival (PFS) at 24 weeks (wks). D 70 mg BID was given orally. CT scans were obtained every 2 months. Pre- and posttreatment plasma VEGF, PDGFβ, and serum CSF-1 and mesothelin-related protein were collected. Tumor was evaluated for expression of EphA2 and PDGFRβ. RESULTS: 46 pts enrolled at 12 sites 9/07-8/09, 35 are evaluable for PFS, 22 for response, and 46 for toxicity. Pt characteristics: Male 72%; median age 68 (range 35, 81); PS 0 41%; epithelial histology 72%, pleural 76%. Median cycles given 2 (range 1-8). The starting dose was reduced to 50 mg BID after the first 23 pts enrolled because 50% of the first 12 pts enrolled had AE grade 3. Grade 3/4 toxicities (% pts): anemia 2%, fatigue 11%, pleural effusion 9%, pericardial effusion 2%, pneumonitis 2%, hypoxia 2%, nausea 4%, hyponatremia 7%, hypophosphatemia 2%.There were 3 grade 5 toxicities: 1 ARDS, 1 respiratory failure, 1 unknown. Efficacy: 24-week PFS rate 15% (95% CI 6%, 29%), median PFS 8.3 wks (7.7, 10.3), median overall survival 20.7 wks (11.4, 28.3), partial response 0%; stable disease 20%. CONCLUSIONS: Dasatinib is inactive in previously-treated MM; the 70 mg dose is poorly tolerated. Further data on biologic correlates will be presented.