Hypertension (HTN) as a potential biomarker of efficacy in patients (pts) with gastrointestinal stromal tumor (GIST) treated with sunitinib (SU).

Abstract

38 Background: HTN is a class effect of VEGF signaling pathway inhibitors. SU is a multitargeted inhibitor of VEGFRs and other receptor tyrosine kinases. Associations between SU-induced HTN and efficacy endpoints (OS, PFS, TTP, and ORR) in pts with imatinib-resistant/intolerant GIST from 2 prospective clinical trials were investigated retrospectively. Methods: This analysis included pooled data from 319 pts who received SU and had post-baseline blood pressure (BP) data available. Tumor response data were based on investigator assessments. Most pts (87%) received SU 50 mg/d on the standard 4-wk-on/2-wk-off schedule. BP was measured on the first and last day of dosing in each treatment cycle at a minimum. HTN was defined as max or mean SBP ≥ 140 or DBP ≥ 90 mmHg. OS, PFS, and TTP were estimated by Kaplan—Meier methods and compared between pts with vs. without HTN using the log-rank test. The influence of prognostic risk factors was analyzed using a Cox proportional hazards model. Results: 233 and 187 pts (73% and 59%) had ≥ 1 HTN episode as defined by max SBP and DBP, respectively. Efficacy results significantly favored pts who developed HTN on SU based on max SBP or DBP (eg, median OS for pts with HTN [max SBP] was 89.4 weeks vs. 53.1 weeks for pts without HTN [p = 0.0001]). Using HTN onset as a time-dependent covariate, HTN defined by max DBP was a significant predictor of prolonged TTP and PFS, and HTN defined by both max SBP and DBP was a significant predictor of prolonged OS (p < 0.05). In multivariate analysis, HTN defined by max SBP or DBP was a significant independent predictor of improved OS, PFS, and TTP (p < 0.0001). Analysis of any-grade and grade ≥3 cerebrovascular, ocular, cardiac, and renal AEs in pts with/without HTN is ongoing and will be presented. Clinical outcomes were not compromised in pts treated with anti-HTN medications. Conclusions: SU-associated HTN was significantly and independently associated with improved clinical outcomes, supporting the hypothesis that HTN is a biomarker for antitumor efficacy in pts with GIST treated with SU. Serial BP monitoring and standard use of anti-HTN medications, which were not shown to compromise efficacy, are recommended during SU therapy. [Table: see text]