nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: long-term survival from a phase III trial.

Abstract

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.

• Authors: David Goldstein, Robert Hassan El-Maraghi, Pascal Hammel, Volker Heinemann, Volker Kunzmann, Javier Sastre, Werner Scheithauer, Salvatore Siena, Josep Tabernero, Luis Teixeira, Giampaolo Tortora, Jean-Luc Van Laethem, Rosemary Young, Darryl Neil Penenberg, Brian Lu, Alfredo Romano, Daniel D Von Hoff
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 107 Issue 2 (Feb 2015) ISSN: 1460-2105 [Electronic] United States
• PMID: 25638248 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• 130-nm albumin-bound paclitaxel
• Albumins
• Antigens, Tumor-Associated, Carbohydrate
• Biomarkers, Tumor
• carbohydrate antigen 199, human
• Deoxycytidine
• Paclitaxel
• Gemcitabine

Topics

• Adenocarcinoma (drug therapy, mortality, secondary)
• Adult
• Aged
• Albumins (administration & dosage, adverse effects)
• Antigens, Tumor-Associated, Carbohydrate (blood)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Biomarkers, Tumor (blood)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• International Cooperation
• Kaplan-Meier Estimate
• Liver Neoplasms (drug therapy, mortality, secondary)
• Lymphocytes (drug effects)
• Male
• Middle Aged
• Neutrophils (drug effects)
• Paclitaxel (administration & dosage, adverse effects)
• Pancreatic Neoplasms (drug therapy, mortality, pathology)
• Prognosis
• Treatment Outcome
• Gemcitabine