FINAL RESULTS OF A PHASE II STUDY OF SUNITINIB AS SECOND LINE THERAPY OF MALIGNANT PLEURAL MESOTHELIOMA (MPM)

7036 Background: There is no standard second-line therapy for progressive MPM. Sunitinib is a multi-targeted tyrosine kinase inhibitor of rational targets in MPM including VEGFR and PDGFR. We tested the safety and efficacy of second-line sunitinib in MPM. Methods: Eligible consenting patients (pts) had progressive MPM during or after first-line platinum/antimetabolite, ECOG PS 0-1, adequate organ function, and measurable disease. Treatment: sunitinib 50 mg/day ×28d q6 weeks. Primary endpoint: objective response (OR) defined by either a). Modified RECIST Criteria (MRC) on CT scan or b) metabolic response on FDG-PET in pts without prior talc pleurodesis (J Nuc Med (48) 1449-58; 2007). Imaging was performed at baseline and after cycles 1, 2, and every 2 cycles thereafter; most PET imaging was during treatment break. Simon's 2 stage design: 2 responses in the first 23 pts and 5 responses in 51 assessable pts gave α = 0.05, β = 0.1 assuming an OR of 20% to be of interest. Results: From 05/06 to 12/09 53 eligible pts were accrued: 51 assessable for response on CT; 20 without pleurodesis assessable on FDG-PET. Demographics: M/F (44/9); median age 64 (range 45 - 81); histology epithelial/sarcomatoid/mixed/unknown (37:1:9:6). ECOG PS 0/1 (15:38). Prior platinum with pemetrexed/gemcitabine(79%/21%). Best MRC response: CR 0; PR 5 (10%); SD 33 (66%); PD 12 (24%). Metabolic response: 7/20 assessable (35%), 1 also with CT PR; 4 with CT minor response. Total protocol-defined response 11/51 (22%, 95% CI 11%-33%). Median OS was 6.7 months. Median TTP was 3.4 months. Total cycles given: 114 (median 2, range 1-6); 3 pts remain on S. Adverse events (number pts experiencing;%): Grade 3/4: thrombocytopenia (3;6%), neutropenia (2;4%); Grade 3: fatigue (11;21%,), anorexia (3;6%), nausea (2;4%). 15/53 required dose reduction. There was one possible treatment- related death from pulmonary infiltrates and respiratory failure, and one grade 4 pneumonitis. Four pts developed increasing pleural effusions or ascites without other radiologic evidence of PD. Conclusions: Sunitinib has modest activity in previously treated MPM; testing at a continuous lower dose may be warranted to ameliorate toxicity. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Australia