Treatment-related Hypertension as a Pharmacodynamic Biomarker for the Efficacy of Bevacizumab in Advanced Pancreas Cancer: A Pooled Analysis of 4 Prospective Trials of Gemcitabine-based Therapy With Bevacizumab. (December 2016)

• Record Type: Journal Article
• Authors: Pant, Shubham; Martin, Ludmila K.; Geyer, Susan; Wei, Lai; Van Loon, Katherine; Sommovilla, Nili; Zalupski, Mark; Iyer, Renuka; Fogelman, David; Ko, Andrew H.; Bekaii-Saab, Tanios
• Is Part Of: American journal of clinical oncology. Volume 39:Number 6(2016)
• Publication Date: 2016-12
• Subjects: pancreas cancer -- pharmacodynamic marker -- hypertension -- bevacizumab; Cancer -- Treatment -- Periodicals; Oncology -- Periodicals; Tumors -- Periodicals; 616.994005
• DOI: 10.1097/COC.0000000000000108
• Languages: English
• ISSNs: 0277-3732

Abstract

Abstract : Purpose: Phase III studies of bevacizumab in advanced pancreas cancer (APCA) demonstrated no improvement in outcome. No validated biomarkers for bevacizumab efficacy exist. We evaluated bevacizumab-related hypertension (B-HTN) as a biomarker in APCA patients in a pooled analysis from 4 prospective clinical trials of gemcitabine-based therapy combined with bevacizumab. Materials and Methods: Data were collected from individual databases from 4 prospective, single-arm phase II trials. Patients were grouped according to B-HTN or no hypertension (HTN), and patients with HTN were further grouped according to highest Common Terminology Criteria for Adverse Events grade of HTN: grade 1-2 or grade 3-4. Clinical outcomes of overall survival, time to progression, overall response rate (ORR), and disease control rate (ORR+SD>16 wk) were compared. Results: A total of 163 patients with stage IV APCA and Eastern Cooperative Oncology Group 0-1 were included. Median age was 59 years (range, 33 to 85 y). Thirty-four patients had B-HTN, and 129 patients had no HTN. Prognostic factors were balanced between groups. Patients with any grade B-HTN had a significantly improved median overall survival (13.1 vs. 8.1 mo, P =0.0006), median time to tumor progression (7.6 vs. 5.5 mo, P =0.0074), ORR (47% vs. 16%, P =0.0001), and disease control rate (85% vs. 59%, P =0.004). There were no differences in outcomes according to HTN grade (1-2 [N=16] vs. 3-4 [N=18]). Conclusions: APCA patients who develop any grade of B-HTN appear to derive benefit from bevacizumab. Additional investigation is needed to identify subgroups of patients who develop B-HTN and are more likely to benefit from bevacizumab.