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

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)614-618
Number of pages5
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume39
Issue number6
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

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gemcitabine
Pancreatic Neoplasms
Biomarkers
Hypertension
Therapeutics
Bevacizumab
Survival

Keywords

  • bevacizumab
  • hypertension
  • pancreas cancer
  • pharmacodynamic marker

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 39, No. 6, 01.01.2016, p. 614-618.

Research output: Contribution to journalArticle

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. / 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. In: American Journal of Clinical Oncology: Cancer Clinical Trials. 2016 ; Vol. 39, No. 6. pp. 614-618.
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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.",
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T1 - Treatment-related Hypertension as a Pharmacodynamic Biomarker for the Efficacy of Bevacizumab in Advanced Pancreas Cancer

T2 - A Pooled Analysis of 4 Prospective Trials of Gemcitabine-based Therapy with Bevacizumab

AU - Pant, Shubham

AU - Martin, Ludmila K.

AU - Geyer, Susan

AU - Wei, Lai

AU - Van Loon, Katherine

AU - Sommovilla, Nili

AU - Zalupski, Mark

AU - Iyer, Renuka

AU - Fogelman, David

AU - Ko, Andrew H.

AU - Bekaii-Saab, Tanios

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N2 - 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.

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KW - pancreas cancer

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