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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

Pant, Shubham MD; Martin, Ludmila K. MD; Geyer, Susan PhD; Wei, Lai PhD; Van Loon, Katherine MD, MPH; Sommovilla, Nili MD; Zalupski, Mark MD; Iyer, Renuka MD; Fogelman, David MD; Ko, Andrew H. MD; Bekaii-Saab, Tanios MD

American Journal of Clinical Oncology: December 2016 - Volume 39 - Issue 6 - p 614–618
doi: 10.1097/COC.0000000000000108
Original Articles: Gastrointestinal

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.

*Department of Oncology, Oklahoma University, Oklahoma City, OK

Department of Internal Medicine, The Ohio State University, Columbus, OH

Department of Internal Medicine, University of California, San Francisco, CA

§Mount Sinai School of Medicine, One Gustave Levy Place, New York

Roswell Park Cancer Institute, Buffalo, NY

1500 E Medical Center Dr, University of Michigan, Ann Arbor, MI

#MD Anderson Cancer Center, Houston, TX

T.B.-S. is a compensated consultant for Genentech and Sanofi-Aventis. A.H.K. is a compensated consultant for Genentech and has received prior honoraria. S.P. received prior honoraria from Genentech. R.I. discloses research funding from Genentech. The remaining authors declare no conflicts of interest.

Reprints: Tanios Bekaii-Saab, MD, The Ohio State University, A454 Starling-Loving Hall, 320 W 10th Ave, Columbus, OH 43210. E-mail: Tanios.Saab@osumc.edu.

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