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Evaluating health-related quality-of-life therapeutic effectiveness in a clinical trial with extensive nonignorable missing data and heterogeneous response: results from a phase III randomized trial of gemcitabine plus paclitaxel versus paclitaxel monotherapy in patients with metastatic breast cancer

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Abstract

Purpose

This manuscript presents health-related quality of life (HRQL) results from a phase III trial of gemcitabine-paclitaxel (GT) versus paclitaxel (T) in metastatic breast cancer patients.

Methods

Patients completed the Rotterdam Symptom Checklist (RSCL) and Brief Pain Inventory (BPI) at baseline and at the end of each cycle. Sensitivity analyses for six longitudinal pattern mixture models (PMMs) assessed potential bias due to informative dropout. Cumulative probability plots with 50% confidence intervals indicated the proportion of patients whose HRQL was likely to improve, decline, or stay the same.

Results

Sensitivity analyses addressing nonignorable missing RSCL data included 351 patients. The mean RSCL global HRQL score for GT was significantly and consistently better than that for T (all PMMs P < 0.040). The slope estimate of 1.5 points (100-point scale) per cycle from one PMM translated to a clinically significant 9-point improvement over six cycles with GT versus T. For GT, ~25% of patients were more likely than not to have improved HRQL, whereas that proportion for T was ~5%. PMMs showed no consistent treatment arm differences for BPI or other RSCL outcomes.

Conclusions

Adding gemcitabine to paclitaxel for the treatment of metastatic breast cancer is more likely to improve global HRQL over time compared to monotherapy treatment.

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Abbreviations

BPI:

Brief Pain Inventory

GT:

Gemcitabine-paclitaxel

HRQL:

Health-related quality of life

MNAR:

Missing not at random

PMM:

Pattern mixture models

RSCL:

Rotterdam Symptom Checklist

T:

Paclitaxel

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Acknowledgments

The authors gratefully acknowledge the participation of the patients in this trial who completed questionnaires, the study personnel at participating institutions, and the investigators who enrolled patients on the trial. The authors also acknowledge Mary Dugan Wood, Lorinda Simms, Yun Ding, Pete Fairfield, Mark Blitzer, and Linda Massey for their assistance in preparing this manuscript. This research was funded by Eli Lilly and Company.

Author information

Authors and Affiliations

  1. Fred Hutchinson Cancer Research Center/M3-C102, 1100 Fairview Avenue North, P.O. Box 19024, Seattle, WA, 98109-1024, USA

    Carol M. Moinpour & Gary W. Donaldson

  2. University of Utah, Salt Lake City, UT, USA

    Gary W. Donaldson

  3. Eli Lilly and Company, Indianapolis, IN, USA

    Astra M. Liepa & Allen S. Melemed

  4. Baylor-Sammons Cancer Center, Dallas, TX, USA

    Joyce O’Shaughnessy

  5. Loyola University Chicago Medical Center, Maywood, IL, USA

    Kathy S. Albain

Authors
  1. Carol M. Moinpour
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  2. Gary W. Donaldson
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  3. Astra M. Liepa
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  4. Allen S. Melemed
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  5. Joyce O’Shaughnessy
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  6. Kathy S. Albain
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Correspondence to Carol M. Moinpour.

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Moinpour, C.M., Donaldson, G.W., Liepa, A.M. et al. Evaluating health-related quality-of-life therapeutic effectiveness in a clinical trial with extensive nonignorable missing data and heterogeneous response: results from a phase III randomized trial of gemcitabine plus paclitaxel versus paclitaxel monotherapy in patients with metastatic breast cancer. Qual Life Res 21, 765–775 (2012). https://doi.org/10.1007/s11136-011-9999-z

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  • DOI: https://doi.org/10.1007/s11136-011-9999-z

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