Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma

Research output: Contribution to journalArticle

Authors

  • P. G. Corrie
  • W. Qian
  • B. Basu
  • J. W. Valle
  • S. Falk
  • C. Lwuji
  • H. Wasan
  • D. Palmer
  • M. Scott-brown
  • J. Wadsley
  • S. Arif
  • J. Bridgewater
  • D. Propper
  • R. Gillmore
  • A. Gopinathan
  • R. Skells
  • P. Bundi
  • R. Brais
  • K. Dalchau
  • L. Bax
  • A. Chhabra
  • A. Machin
  • A. Dayim
  • K. Mcadam
  • S. Cummins
  • L. Wall
  • R. Ellis
  • A. Anthoney
  • J. Evans
  • C. Isherwood
  • A. Neesse
  • D. Tuveson
  • D. I. Jodrell

Colleges, School and Institutes

Abstract

Background: Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial. Methods: Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers. Results: In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47–0.95, p = 0.022) and ORR (52% versus 31%, p = 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65–1.33, p = 0.70). CTCAE Grade ≥3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13–0.70). Conclusions: SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS. Clinical trial registration: ISRCTN71070888; ClinialTrials.gov (NCT03529175).

Details

Original languageEnglish
Pages (from-to)1760–1768
Number of pages9
JournalBritish Journal of Cancer
Volume122
Issue number12
Early online date30 Apr 2020
Publication statusPublished - 9 Jun 2020

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