title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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]).
  
  
  
  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.
authors: *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.
authors: Shubham
authors: S
authors: Pant
authors: Ludmila K
authors: LK
authors: Martin
authors: Susan
authors: S
authors: Geyer
authors: Lai
authors: L
authors: Wei
authors: Katherine
authors: K
authors: Van Loon
authors: Nili
authors: N
authors: Sommovilla
authors: Mark
authors: M
authors: Zalupski
authors: Renuka
authors: R
authors: Iyer
authors: David
authors: D
authors: Fogelman
authors: Andrew H
authors: AH
authors: Ko
authors: Tanios
authors: T
authors: Bekaii-Saab
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D011446:Prospective Studies; D018570:Risk Assessment; D016037:Single-Blind Method; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D003841:Deoxycytidine; D000068258:Bevacizumab; D000093542:Gemcitabine