title: Positron emission tomography response evaluation from a randomized phase III trial of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients with metastatic adenocarcinoma of the pancreas.
abstract: BACKGROUND
  In the phase III MPACT trial, nab-paclitaxel plus gemcitabine (nab-P + Gem) demonstrated superior efficacy versus Gem alone for patients with metastatic pancreatic cancer. We sought to examine the feasibility of positron emission tomography (PET) and to compare metabolic response rates and associated correlations with efficacy in the MPACT trial.
  
  
  METHODS
  Patients with previously untreated metastatic adenocarcinoma of the pancreas were randomized 1:1 to receive nab-P + Gem or Gem alone. Treatment continued until disease progression by RECIST or unacceptable toxicity.
  
  
  RESULTS
  PET scans were carried out on the first 257 patients enrolled at PET-equipped centers (PET cohort). Most patients (252 of 257) had ≥2 PET-avid lesions, and median maximum standardized uptake values at baseline were 4.6 and 4.5 in the nab-P + Gem and Gem-alone arms, respectively. In a pooled treatment arm analysis, a metabolic response by PET (best response at any time during study) was associated with longer overall survival (OS) (median 11.3 versus 6.9 months; HR, 0.56; P < 0.001). Efficacy results within each treatment arm appeared better for patients with a metabolic response. The metabolic response rate (best response and week 8 response) was higher for nab-P + Gem (best response: 72% versus 53%, P = 0.002; week 8: 67% versus 51%; P = 0.014). Efficacy in the PET cohort was greater for nab-P + Gem versus Gem alone, including for OS (median 10.5 versus 8.4 months; hazard ratio [HR], 0.71; P = 0.009) and ORR by RECIST (31% versus 11%; P < 0.001).
  
  
  CONCLUSIONS
  Pancreatic lesions were PET avid at baseline, and the rate of metabolic response was significantly higher for nab-P + Gem versus Gem alone at week 8 and for best response during study. Having a metabolic response was associated with longer survival, and more patients experienced a metabolic response than a RECIST-defined response.
  
  
  BACKGROUND
  NCT00844649.
authors.affiliation: Division of Hematology/Oncology, Mayo Clinic, Scottsdale, USA ramanathan.ramesh@mayo.edu.
authors.forename: R K
authors.initials: RK
authors.lastname: Ramanathan
authors.affiliation: Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Goldstein
authors.affiliation: Diagnostic Radiology, Scottsdale Medical Imaging, Ltd, Scottsdale.
authors.forename: R L
authors.initials: RL
authors.lastname: Korn
authors.affiliation: Hematology/Oncology, NYU Langone Arena Oncology, Lake Success, USA.
authors.forename: F
authors.initials: F
authors.lastname: Arena
authors.affiliation: Provencial Health Services Authority, BC Cancer Agency, Vancouver, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Moore
authors.affiliation: Falck Division of Oncology, Department of Oncology and Hematology, Niguarda Cancer Center, Ospedale Niguarda Ca' Granda and Università degli Studi di Millano, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Siena
authors.affiliation: Department of Medical Oncology, Hôpital Saint-Antoine, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Teixeira
authors.affiliation: Department 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: University Clinic of Brussels, Hôpital Erasme, Brussels, Belgium.
authors.forename: J-L
authors.initials: JL
authors.lastname: Van Laethem
authors.affiliation: Biostatistics and Research and Design, Celgene Corporation, Summit.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.affiliation: Biostatistics and Research and Design, Celgene Corporation, Summit.
authors.forename: D
authors.initials: D
authors.lastname: McGovern
authors.affiliation: Biostatistics and Research and Design, Celgene Corporation, Summit.
authors.forename: B
authors.initials: B
authors.lastname: Lu
authors.affiliation: Clinical Research, Translational Genomics Research Institute and Honor Health, Scottsdale, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Von Hoff
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D049268:Positron-Emission Tomography; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine
keywords: gemcitabine; metabolic response; nab-paclitaxel; pancreatic cancer; positron emission tomography