Quality-adjusted survival with combination nab-paclitaxel + gemcitabine vs gemcitabine alone in metastatic pancreatic cancer: a Q-TWiST analysis

Abstract

Objectives:

To use the Quality-Adjusted Time Without Symptoms or Toxicities (Q-TWiST) methodology to compare the quality-of-life and survival benefits associated with the combination of albumin-bound (nab)-paclitaxel and gemcitabine vs gemcitabine alone in the first-line treatment of metastatic pancreatic adenocarcinoma.

Methods:

Total survival time through 45 months was partitioned into time before disease progression without toxicity grade ≥3 (TWiST), time with adverse event grade ≥3 (TOX), and time of disease progression (REL). Mean Q-TWiST was calculated by multiplying time spent in each health state by its respective utility (i.e., TWiST = 1.00; TOX/REL = 0.50, 0–1 in sensitivity analyses). Non-parametric bootstrap 95% confidence intervals (CI) were derived to assess the significance of between-treatment differences in TOX, TWiST, REL, and Q-TWiST. A relative gain in Q-TWiST (vs mean overall survival of gemcitabine) of ≥10% and ≥15% was defined as clinically important and clearly clinically important, respectively.

Results:

Patients on nab-paclitaxel + gemcitabine spent a significantly longer time in every state and experienced significantly greater overall Q-TWiST (+1.7 months [95% CI = 0.8, 2.7]) than those receiving gemcitabine alone (8.2 months [95% CI = 7.5, 8.9] vs 6.5 months [95% CI = 5.8, 7.0]), assuming base-case utilities of TOX/REL = 0.50. This Q-TWiST gain ranged from 1.0 month (95% CI = 0.1, 1.9), when REL/TOX utilities were both 0, to 2.5 months (95% CI = 1.3, 3.7), when REL/TOX utilities were both 1. Relative gains in Q-TWiST were 21% in favor of nab-paclitaxel + gemcitabine in the base case, and ranged from 12–30% in sensitivity analyses.

Conclusions:

There are limitations to Q-TWiST analyses, e.g., imprecision when defining duration/severity of TOX and lack of prospective collection of utilities. This analysis addressed these issues via sensitivity analyses and conservative assumptions to show that nab-paclitaxel + gemcitabine results in statistically significant and clinically important gains in quality-adjusted survival, when compared to gemcitabine alone, in treatment-naive metastatic pancreatic adenocarcinoma patients.

Keywords::

• Albumin-bound (nab)-paclitaxel
• Metastatic pancreatic adenocarcinoma
• Q-TWiST
• Quality-adjusted survival
• Pancreatic neoplasms

Transparency

Declaration of funding

This study was sponsored in part by Celgene Corporation, Summit, NJ, which manufactures and commercializes nab-paclitaxel. Besides funding, Celgene Corporation provided access to the patient-level data of the MPACT trial to conduct the present analysis.

Declaration of financial/other relationships

Dr Michele Reni, MD has disclosed that he has received grants from and is an advisor to Celgene, and is a physician at the San Raffaele Scientific Institute, Milan. Yin Wan, Caitlyn Solem, Ji Xiang, and Marc Botteman are employees of Pharmerit International, an independent contract research organization that received research funding from Celgene. Scott Whiting is an employee of Celgene Corporation. JME peer reviewers on this manuscript have received an honorarium from JME for their review work, but have no other relevant financial relationships to disclose.

Acknowledgments

The authors wish to thank anonymous reviewers for providing valuable comments on this manuscript. The authors thank Joan Hudson from ProEd Communications Inc. for providing compensated editorial support on the manuscript.

Notice of Correction:

The version of this article published online ahead of print on 21 March 2014 contained errors in Figure 1. The publishers apologise for these errors, which were introduced during the typesetting process. The errors have been corrected in this version of the article.