title: CA19-9 decrease at 8 weeks as a predictor of overall survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer.
abstract: BACKGROUND
  A phase I/II study and subsequent phase III study (MPACT) reported significant correlations between CA19-9 decreases and prolonged overall survival (OS) with nab-paclitaxel plus gemcitabine (nab-P + Gem) treatment for metastatic pancreatic cancer (MPC). CA19-9 changes at week 8 and potential associations with efficacy were investigated as part of an exploratory analysis in the MPACT trial.
  
  
  METHODS
  Untreated patients with MPC (N = 861) received nab-P + Gem or Gem alone. CA19-9 was evaluated at baseline and every 8 weeks.
  
  
  RESULTS
  Patients with baseline and week-8 CA19-9 measurements were analyzed (nab-P + Gem: 252; Gem: 202). In an analysis pooling the treatments, patients with any CA19-9 decline (80%) versus those without (20%) had improved OS (median 11.1 versus 8.0 months; P = 0.005). In the nab-P + Gem arm, patients with (n = 206) versus without (n = 46) any CA19-9 decrease at week 8 had a confirmed overall response rate (ORR) of 40% versus 13%, and a median OS of 13.2 versus 8.3 months (P = 0.001), respectively. In the Gem-alone arm, patients with (n = 159) versus without (n = 43) CA19-9 decrease at week 8 had a confirmed ORR of 15% versus 5%, and a median OS of 9.4 versus 7.1 months (P = 0.404), respectively. In the nab-P + Gem and Gem-alone arms, by week 8, 16% (40/252) and 6% (13/202) of patients, respectively, had an unconfirmed radiologic response (median OS 13.7 and 14.7 months, respectively), and 79% and 84% of patients, respectively, had stable disease (SD) (median OS 11.1 and 9 months, respectively). Patients with SD and any CA19-9 decrease (158/199 and 133/170) had a median OS of 13.2 and 9.4 months, respectively.
  
  
  CONCLUSIONS
  This analysis demonstrated that, in patients with MPC, any CA19-9 decrease at week 8 can be an early marker for chemotherapy efficacy, including in those patients with SD. CA19-9 decrease identified more patients with survival benefit than radiologic response by week 8.
authors.affiliation: Department of Medicine/Oncology, University of Washington, Fred Hutchinson Cancer Research Center, Seattle gchiorea@uw.edu.
authors.forename: E G
authors.initials: EG
authors.lastname: Chiorean
authors.affiliation: HonorHealth and The Translational Genomics Research Institute (TGen), Scottsdale, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Von Hoff
authors.affiliation: Department of Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Reni
authors.affiliation: Department of Oncology, NYU Langone Arena Oncology, Lake Success.
authors.forename: F P
authors.initials: FP
authors.lastname: Arena
authors.affiliation: Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Nashville.
authors.forename: J R
authors.initials: JR
authors.lastname: Infante
authors.affiliation: Cancer Center of Excellence, University of Massachusetts Medical School, Worcester.
authors.forename: V G
authors.initials: VG
authors.lastname: Bathini
authors.affiliation: UAB Comprehensive Cancer Center, Birmingham, USA.
authors.forename: T E
authors.initials: TE
authors.lastname: Wood
authors.affiliation: Mater Private Centre for Haematology & Oncology, South Brisbane, Australia.
authors.forename: P N
authors.initials: PN
authors.lastname: Mainwaring
authors.affiliation: Department of Oncology, Genesis Cancer Center, Hot Springs, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Muldoon
authors.affiliation: Southern Medical Day Care Centre, Wollongong, Australia.
authors.forename: P R
authors.initials: PR
authors.lastname: Clingan
authors.affiliation: Medizinische Klinik und Poliklinik II, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Kunzmann
authors.affiliation: HonorHealth and The Translational Genomics Research Institute (TGen), Scottsdale, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Ramanathan
authors.affiliation: Medical of Medical Oncology, Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Tabernero
authors.affiliation: Department of Oncology, Prince of Wales Hospital, Sydney, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Goldstein
authors.affiliation: Celgene Corporation, Summit, USA.
authors.forename: D
authors.initials: D
authors.lastname: McGovern
authors.affiliation: Celgene Corporation, Summit, USA.
authors.forename: B
authors.initials: B
authors.lastname: Lu
authors.affiliation: Celgene Corporation, Summit, USA.
authors.forename: A
authors.initials: A
authors.lastname: Ko
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000418:Albumins / Q000008:administration & dosage*; D054316:Biomarkers, Pharmacological / Q000097:blood; D018395:CA-19-9 Antigen / Q000097:blood*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D054316:Biomarkers, Pharmacological; D018395:CA-19-9 Antigen; D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine
keywords: CA19-9; MPACT; chemotherapy; nab-paclitaxel; pancreatic cancer