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

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. BaxA. Chhabra, A. Machin, A. Dayim, K. Mcadam, S. Cummins, L. Wall, R. Ellis, A. Anthoney, J. Evans, Y. T. Ma, C. Isherwood, A. Neesse, D. Tuveson, D. I. Jodrell

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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).

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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