Skip to main content

Coagulation factors in citrated plasma predict for benefit from bevacizumab (B) in patients with advanced pancreatic cancer (APC): Results from CALGB 80303 (Alliance).

Publication ,  Conference
Clarke, JM; Pang, H; Starr, MD; Hatch, AJ; Kindler, HL; O'Reilly, EM; Innocenti, F; Venook, AP; Hurwitz, H; Nixon, AB
Published in: Journal of Clinical Oncology
January 20, 2015

306 Background: CALGB 80303 evaluated gemcitabine (G) in combination with either B or placebo (P) in 602 patients (pts) with APC. No significant difference in overall survival (OS) between treatment arms was observed. Previously, plasma EDTA samples from CALGB 80303 were analyzed and potential predictive biomarkers for B were identified. This follow-up analysis evaluated citrated plasma samples for circulating proteins related to matrix remodeling and coagulation. Methods: Multiplex ELISA analysis was employed to assess the following circulating factors: E-selectin, matrix metalloprotease (MMP) 2, MMP9, von Willebrand factor (vWF), D-dimer, thrombospondin 1, and tissue factor (TF). Thrombin-antithrombin complex (TAT) was analyzed using a standard enzyme immunoassay. Prognostic characteristics were determined by associating baseline values with OS using a Cox model. Predictive markers were identified with inclusion of a treatment by marker interaction term. Results: Baseline citrated plasma samples from 109 pts were included in this analysis (59 pts G+P; 50 pts G+B). Negative prognostic factors for OS were identified, including E-selectin (p <0.01) for patients receiving G-based therapy, and E-selectin, TF, and vWF (p <0.05) in pts receiving G+P. Potential biomarkers predicting for OS benefit from B were also identified. Pts with low (< median) levels of TAT (interaction p=0.034) exhibited a median OS of 6.0 months (mo) vs. 8.3 mo (HR=0.49; 95%CI 0.28-0.88) when receiving G+P vs. G+B, respectively. Furthermore, pts with elevated levels of TF (>Q3) were found to benefit from B (interaction p=0.021), with median OS of 4.3 mo vs 4.8 mo (HR=0.44;95%CI 0.18-1.08), respectively. Longitudinal analysis of samples collected at baseline and at cycle 3 indicated that only vWF changed in pts receiving G+P, with an increase in vWF (p<0.05). Conclusions: In patients with APC, baseline levels of TAT and TF were identified as potential predictors of benefit from B. These data emphasize the importance of coagulation factors in modulating tumor angiogenesis. The potential predictive value of these factors warrants further validation.

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

January 20, 2015

Volume

33

Issue

3_suppl

Start / End Page

306 / 306

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Clarke, J. M., Pang, H., Starr, M. D., Hatch, A. J., Kindler, H. L., O’Reilly, E. M., … Nixon, A. B. (2015). Coagulation factors in citrated plasma predict for benefit from bevacizumab (B) in patients with advanced pancreatic cancer (APC): Results from CALGB 80303 (Alliance). In Journal of Clinical Oncology (Vol. 33, pp. 306–306). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2015.33.3_suppl.306
Clarke, Jeffrey Melson, Herbert Pang, Mark D. Starr, Ace Joseph Hatch, Hedy Lee Kindler, Eileen Mary O’Reilly, Federico Innocenti, Alan P. Venook, Herbert Hurwitz, and Andrew B. Nixon. “Coagulation factors in citrated plasma predict for benefit from bevacizumab (B) in patients with advanced pancreatic cancer (APC): Results from CALGB 80303 (Alliance).” In Journal of Clinical Oncology, 33:306–306. American Society of Clinical Oncology (ASCO), 2015. https://doi.org/10.1200/jco.2015.33.3_suppl.306.
Clarke JM, Pang H, Starr MD, Hatch AJ, Kindler HL, O’Reilly EM, et al. Coagulation factors in citrated plasma predict for benefit from bevacizumab (B) in patients with advanced pancreatic cancer (APC): Results from CALGB 80303 (Alliance). In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2015. p. 306–306.
Clarke, Jeffrey Melson, et al. “Coagulation factors in citrated plasma predict for benefit from bevacizumab (B) in patients with advanced pancreatic cancer (APC): Results from CALGB 80303 (Alliance).Journal of Clinical Oncology, vol. 33, no. 3_suppl, American Society of Clinical Oncology (ASCO), 2015, pp. 306–306. Crossref, doi:10.1200/jco.2015.33.3_suppl.306.
Clarke JM, Pang H, Starr MD, Hatch AJ, Kindler HL, O’Reilly EM, Innocenti F, Venook AP, Hurwitz H, Nixon AB. Coagulation factors in citrated plasma predict for benefit from bevacizumab (B) in patients with advanced pancreatic cancer (APC): Results from CALGB 80303 (Alliance). Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2015. p. 306–306.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

January 20, 2015

Volume

33

Issue

3_suppl

Start / End Page

306 / 306

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences