Citation: British Journal of Cancer. 2020, 122(12), 1760-68. Epub 2020 Apr 30.
Author: 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, Y T Ma, C Isherwood, A Neesse, D Tuveson, D I Jodrell
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).
Link to PubMed record
