Abstract 4628: Acid suppression therapy impairs sunitinib efficacy in renal cell cancer (RCC)

Abstract

Background: Sunitinib, a tyrosine kinase inhibitor (TKI), is standard therapy in metastatic RCC (mRCC). Developing side effects may be a marker of sufficient treatment doses. But as an oral drug, a potential issue is pH-dependent absorption. Recent evidence suggests TKI plasma levels can be altered by concomitant use of acid suppression therapy. Given gastroesophageal reflux disease (GERD) is a side effect of sunitinib and has high prevalence, this study aims to determine if coadministration of acid suppression therapy and sunitinib affected clinical outcomes in mRCC. Methods: mRCC patients treated with sunitinib between two cancer centres from 2007 to 2013 were retrospectively reviewed. Patients were excluded if they received ≤ 1 week of treatment. Aside from demographics and histologic subtype, Memorial Sloan Kettering Cancer Center (MSKCC) and Heng prognostic scores were calculated. Sunitinib dose reductions were noted to divide patients into those that received 50 mg, 37.5 mg, or 25 mg. Patients were identified as receiving acid suppression if their pharmacy records included a proton pump inhibitor (PPI). Patients were considered taking these medications concomitantly if dates for PPI overlapped their sunitinib prescription by ≥ 20% of treatment duration. Progression free survival (PFS) and overall survival (OS) were primary endpoints. Results: Of 383 mRCC patients identified, 379 were eligible for review. Median age was 62.7 years, 276 male, and 103 female. 286 had clear-cell histology and 93 non-clear cell. 47 patients were identified as continuously taking concomitant PPI, 146 intermittently, and 186 none at all. Median PFS for continuous, intermittent and no-PPI therapy groups were 4.3 months, 15.0 months, and 5.4 months, respectively (p<0.0001). OS for the three groups were 9.3 months, 34.3 months, and 12.1 months, respectively (p<0.0001). In multivariate analysis considering age, gender, histologic subtype, prior nephrectomy, and Heng score, Cox proportional hazards ratios for PFS and OS between continuous and no-PPI therapy groups were 2.08 (95% CI 1.43-3.05, p=0.0002) and 2.06 (95% CI 1.37-3.11, p=0.0006), respectively. Switching Heng for MSKCC score found similar hazards ratios of 2.06 (95% CI 1.41-3.01, p= 0.0002) and 2.09 (95% CI 1.39-3.14, p=0.0004), respectively. Our study found a trend to improved PFS and OS for those requiring a dose reduction (p=0.08). Effects of PPI therapy were still significant considering dose reductions. Conclusion: This large population based study demonstrates sunitinib outcomes are affected by gastric acidity. Results lend further support that PPI therapy can alter TKI absorption; particularly as the intermittent PPI therapy group performed best suggesting that these patients were likely placed on PPI due to sunitinib toxicity. Consequently, they were effectively dose reduced using PPIs rather than decreasing administration dosage. Citation Format: Michael P. Chu, Vincent Ha, Margaret Ngo, Sunita Ghosh, Carole R. Chambers, Michael B. Sawyer. Acid suppression therapy impairs sunitinib efficacy in renal cell cancer (RCC). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4628. doi:10.1158/1538-7445.AM2014-4628