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

Corrie, P.G. et al. (2020) Scheduling nab-paclitaxel combined with gemcitabine as first line treatment for metastatic pancreatic adenocarcinoma. British Journal of Cancer, 122(12), pp. 1760-1768. (doi: 10.1038/s41416-020-0846-2) (PMID:32350413) (PMCID:PMC7283477)

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: Articles
• Additional Information: Grant funding was provided by Celgene Sarl [Celgene reference number AX-PANC-PI-0101].
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Evans, Professor Jeff
• Authors: Corrie, P.G., Qian, W., Basu, B., Valle, J.W., Falk, S., Iwuji, 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., and Jodrell, D.I.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: British Journal of Cancer
• Publisher: Springer Nature
• ISSN: 0007-0920
• ISSN (Online): 1532-1827
• Published Online: 30 April 2020
• Copyright Holders: Copyright © The Author(s) 2020
• First Published: First published in British Journal of Cancer 122:1760-1768
• Publisher Policy: Reproduced under a Creative Commons Licence