Scheduling Nab-Paclitaxel Combined With Gemcitabine as First-Line Treatment for Metastatic Pancreatic Adenocarcinoma

Corrie, P.G., Qian, W., Basu, B., Valle, J.W., Falk, S., Lwuji, C., Wasan, H., Palmer, D., Scott-Brown, M., Wadsley, J., Arif, S., Bridgewater, J., Propper, D., Gillmore, R., Gopinathan, A., Skells, R., Bundi, P., Brais, R., Dalchau, K., Bax, L., Chhabra, A., Machin, A., Dayim, A., McAdam, K., Cummins, S., Wall, L., Ellis, R., Anthoney, A., Evans, J., Ma, Y.T., Isherwood, C., Neesse, A., Tuveson, D., Jodrell, D. I. (April 2020) Scheduling Nab-Paclitaxel Combined With Gemcitabine as First-Line Treatment for Metastatic Pancreatic Adenocarcinoma. Br J Cancer. ISSN 0007-0920

URL: https://pubmed.ncbi.nlm.nih.gov/32350413/
DOI: 10.1038/s41416-020-0846-2

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).

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders > cancer > drugs and therapies > chemotherapy
diseases & disorders > cancer > cancer types > pancreatic cancer
CSHL Authors:
Communities: CSHL labs > Tuveson lab
CSHL Cancer Center Program > Cellular Communication in Cancer Program
Depositing User: Adrian Gomez
Date: 30 April 2020
Date Deposited: 07 May 2020 15:27
Last Modified: 22 Oct 2020 20:57
Related URLs:
URI: https://repository.cshl.edu/id/eprint/39351

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving