Association of hypertension (HTN) and clinical outcome in a phase II trial of cisplatin (C), pemetrexed (P), and bevacizumab (B) in patients (pts) with untreated malignant mesothelioma.

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e18012 Background: B is a monoclonal antibody targeting VEGF with demonstrated efficacy in several solid tumors. HTN is a common toxicity of VEGF-targeted therapies, including B, and is a potential surrogate marker of activity for these agents. Methods: We performed a retrospective review of serial blood pressures (BP) in MM pts enrolled in a multicenter phase II study of C, P, and B. Eligible pts had unresectable, histologically confirmed MM, no prior chemotherapy, and PS 0-1. Pts received C 75 mg/m2, P 500 mg/m2 and B 15 mg/kg Q21d for 6 cycles, then B Q21d until progression. BP was recorded at baseline and on day 1 of each cycle. HTN was classified according to European Society of Hypertension (ESH) guidelines. Univariate and multivariate regression analyses were performed to identify differential outcomes between hypertensive and nonhypertensive pts. Results: 45 pts were enrolled at 4 centers between 3/06 and 10/09. Preliminary efficacy data has been presented (ASCO 2009; abstract 7578). Median PFS and OS were 6.9 (95% CI, 5.3-7.7) and 15.3 (95% CI, 11.3-23.5) months (mo). Median PFS and OS for pts with grades (G) 0, 1, and 2/3 HTN are in the tables below. Maximum increase in systolic BP (Smax) also predicted for improved PFS (HR 0.95, 95% CI 0.92-0.98, p=0.001) and OS (HR 0.96, 95% CI 0.93-0.99, p=0.015). In multivariate analysis including EORTC risk score, primary site, Smax, and ESH G1, 2, or 3 HTN, only ESH G1, 2 or 3 HTN predicted for improved PFS (HR 0.21, CI 0.06-0.70, p = 0.01) and OS (HR 0.21, CI 0.06-0.75, p = 0.02). Conclusions: In this study of C, P, and B in MM, development of HTN is a possible biomarker for B activity and is a significant predictor of outcome. # total Median PFS (95% CI)(mo) HR (95% CI) p value ESH grade 0 10 3.1 (2.7, 4.7) Reference ESH grade 1 16 7.7 (5.2, 10.8) 0.13 (0.05, 0.38) 0.0002 ESH grade 2, 3 19 7.3 (6.9, 15.9) 0.10 (0.04, 0.29) < 0.0001 # total Median OS (95% CI)(mo) HR (95% CI) p value ESH grade 0 10 7.9 (6.5, 9.3) Reference ESH grade 1 16 Not reached (11.3, ****) 0.27 (0.08, 0.87) 0.03 ESH grade 2, 3 19 15.9 (14.8, 31.3) 0.25 (0.1, 0.62) 0.003 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI, Roche Abbott Laboratories, Genentech, Lilly, Novartis

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