Carbohydrate antigen 19-9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine-containing chemotherapy: a pooled analysis of 6 prospective trials

Cancer. 2013 Jan 15;119(2):285-92. doi: 10.1002/cncr.27734. Epub 2012 Jul 11.

Abstract

Background: Carbohydrate antigen 19-9 (CA19-9) is a widely used biomarker in pancreatic cancer. There is no consensus on the interpretation of the change in CA19-9 serum levels and its role in the clinical management of patients with pancreatic cancer.

Methods: Individual patient data from 6 prospective trials evaluating gemcitabine-containing regimens from 3 different institutions were pooled. CA19-9 values were obtained at baseline and after successive cycles of treatment. The objective of this study was to correlate a decline in CA19-9 with outcomes while undergoing treatment.

Results: A total of 212 patients with locally advanced (n = 50) or metastatic (n = 162) adenocarcinoma of the pancreas were included. Median baseline CA19-9 level was 1077 ng/mL (range, 15-492,241 ng/mL). Groups were divided into those levels below (low) or above (high) the median. Median overall survival (mOS) was 8.7 versus 5.2 months (P = .0018) and median time to progression (mTTP) was 5.8 versus 3.7 months (P = .082) in the low versus high groups, respectively. After 2 cycles of chemotherapy, up to a 5% increase versus ≥ 5% increase in CA19-9 levels conferred an improved mOS (10.3 vs 5.1 months, P = .0022) and mTTP (7.5 vs 3.5 months, P = 0.0005).

Conclusions: In patients who have advanced pancreatic cancer treated with gemcitabine-containing regimens baseline CA19-9 is prognostic for outcome. A decline in CA19-9 after the second cycle of chemotherapy is not predictive of improved mOS or mTTP; thus, CA19-9 decline is not a useful surrogate endpoint in clinical trials. Clinically, a ≥ 5% rise in CA19-9 after 2 cycles of chemotherapy serves as a negative predictive marker.

Publication types

  • Meta-Analysis

MeSH terms

  • Adenocarcinoma / blood*
  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Area Under Curve
  • CA-19-9 Antigen / blood*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / blood*
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • ROC Curve
  • Treatment Outcome

Substances

  • CA-19-9 Antigen
  • Deoxycytidine
  • Gemcitabine