Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma
-
Published:2020-04-30
Issue:12
Volume:122
Page:1760-1768
-
ISSN:0007-0920
-
Container-title:British Journal of Cancer
-
language:en
-
Short-container-title:Br J Cancer
Author:
Corrie P. G., Qian W., Basu B., Valle J. W.ORCID, Falk S., lwuji C., Wasan H., Palmer D., Scott-Brown M., Wadsley J., Arif S., Bridgewater J.ORCID, 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.
Abstract
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).
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology
Reference25 articles.
1. Malvezzi, M., Bertuccio, P., Levi, F., La Vecchia, C. & Negri, E. European cancer mortality predictions for the year 2014. Ann. Oncol. 25, 1650–1656 (2014). 2. Von Hoff, D. D., Ervin, T., Arena, F. P., Chiorean, E. G., Infante, J., Moore, M. et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N. Engl. J. Med. 369, 1691–1703 (2013). 3. Goldstein, D., El-Maraghi, R. H., Hammel, P., Heinemann, V., Kunzmann, V., Sastre, J. et al. Nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial. J. Natl Cancer Inst. 107, 3–10 (2015). 4. Von Hoff, D. D., Ramanathan, R. K., Borad, M. J., Laheru, D. A., Smith, L. S., Wood, T. E. et al. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J. Clin. Oncol. 29, 4548–4554 (2011). 5. Alvarez, R., Musteanu, M., Garcia-garcia, E., Lopez-Casas, P. P., Megias, D., Guerra, C. et al. Stromal disrupting effects of nab-paclitaxel in pancreatic cancer. Br. J. Cancer 109, 926–933 (2013).
Cited by
13 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|