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
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 diseases & disorders > neoplasms 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: | 29 Jan 2024 20:53 |
| PMCID: | PMC7283477 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/39351 |
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