Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma
Authors
Corrie, P. G.Qian, W.
Basu, B.
Valle, Juan 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.
Affiliation
Cambridge University Hospitals NHS Foundation Trust (Addenbrooke's Hospital), Cambridge, UK.Issue Date
2020
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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 0.31Citation
P. G. Corrie, W. Qian, B. Basu, J. W. Valle et al. Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma. Br J Cancer. 2020.Journal
British Journal of CancerDOI
10.1038/s41416-020-0846-2PubMed ID
32350413Additional Links
https://dx.doi.org/10.1038/s41416-020-0846-2Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41416-020-0846-2
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