Medline ® Abstract for Reference 81
nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial.
Goldstein D, El-Maraghi RH, Hammel P, Heinemann V, Kunzmann V, Sastre J, Scheithauer W, Siena S, Tabernero J, Teixeira L, Tortora G, Van Laethem JL, Young R, Penenberg DN, Lu B, Romano A, Von Hoff DD
J Natl Cancer Inst. 2015;107(2) Epub 2015 Jan 31.
BACKGROUND: Positive findings from the phase III MPACT trial led to the regulatory approval of nab-paclitaxel plus gemcitabine as a treatment option for patients with metastatic pancreatic cancer. This report is an update of overall survival (OS) based on longer follow-up.
METHODS: Patients (n = 861) with metastatic pancreatic cancer and a Karnofsky performance status of 70 or greater were randomly assigned one to one to receive nab-paclitaxel + gemcitabine or gemcitabine alone. Efficacy data for this post hoc analysis were collected through May 9, 2013. Exploratory analyses of carbohydrate antigen 19-9 (CA19-9) and neutrophil-to-lymphocyte ratio (NLR) were conducted. The primary efficacy endpoint was OS, which was analyzed for all randomly assigned patients by the Kaplan-Meier method. All statistical tests were two-sided.
RESULTS: The median OS was statistically significantly longer for nab-paclitaxel plus gemcitabine vs gemcitabine alone (8.7 vs 6.6 months, hazard ratio [HR]= 0.72, 95% confidence interval [CI]= 0.62 to 0.83, P<.001). Long-term (>three-year) survivors were identified in the nab-paclitaxel plus gemcitabine arm only (4%). In pooled treatment arm analyses, higher CA19-9 level and NLR at baseline were statistically significantly associated with worse OS. There appeared to be a treatment effect for OS favoring nab-paclitaxel plus gemcitabine over gemcitabine alone in poor-prognosis subgroups defined by these factors (HR = 0.612, P<.001 for CA19-9 level≥median and HR = 0.81, P = .079 for NLR>5).
CONCLUSIONS: These data confirm and extend the primary report of OS, supporting the superior efficacy of nab-paclitaxel plus gemcitabine over gemcitabine alone. Subgroup analyses support the relevance of CA 19-9 and NLR as prognostic markers in metastatic pancreatic cancer.
Prince of Wales Hospital, University of New South Wales, Sydney, NSW, Australia (DG); Royal Victoria Regional Health Centre, Barrie, ON, Canada (RHEM); Hôpital Beaujon, Clichy, France (PH); Klinikum Grosshadern, University of Munich, Munich, Germany (VH); Universitätsklinikum Würzburg, Würzburg, Germany (VK); Hospital Clinico San Carlos, Madrid, Spain (JS); Medizinische Universität Wien, Wien, Austria (WS); Ospedale Niguarda Ca' Granda, Milan, Italy (SS); Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Hôpital Saint Antoine, Paris, France (LT); Azienda Ospedaliera Universitaria Integrata and University of Verona, Verona, Italy (GT); Hôpital Erasme, Brussels, Belgium (JLVL); Royal Hobart Hospital, Hobart, Australia (RY); Celgene Corporation, Summit, NJ (DNP); Celgene Corporation, Summit, NJ (BL); Celgene Corporation, Boudry, Switzerland (AR); Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scott