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Quality of Life in a Randomized Control Trial? Comments Concerning MA 17.

The Breast Cancer Study Group of Institut Curie, Departments of Surgery, Radiation Therapy, Psycho-Oncology, Pathology, Paris, France

To the Editor:

The study by Whelan et al,¹ "Assessment of Quality of Life in MA 17," made a considerable contribution to everyday oncology practice because it demonstrated that prescription of letrozole after 5 years of tamoxifen provides a therapeutic benefit in terms of relapse in the adjuvant treatment of hormone-dependent breast cancer in postmenopausal women.

In parallel, it is also essential to assess the quality of life of patients receiving a long-term treatment that is not devoid of adverse effects. Does this quality-of-life study answer the main questions faced by clinicians? Specifically, in this therapeutic trial, did letrozole induce any adverse effects affecting quality of life, and if so, in what proportion of patients? What was the time course for a given symptom (ie, time to onset, regression, deterioration)? What were the repercussions of the adverse effects of this treatment on compliance, bearing in mind that compliance is probably different in therapeutic trials and in everyday clinical practice?

In this study, compliance was evaluated by the ratio of the number of patients who completed the questionnaires at each time point to the number of patients who were still included in the quality-of-life study (expected), but it would have been preferable to express this ratio with respect to the number of patients initially included in the study (intention-to-treat population²).

For example, at 6 months, 27% of patients (481 of 1,799) in the placebo group and 29% of patients (523 of 1,813) in the letrozole group did not complete the quality-of-life questionnaire. At 36 months, 82% and 81% of the placebo and letrozole patients, respectively, have not completed their questionnaires. Therefore, the study was based on less than 20% of the initial sample. It is not clear whether patients were excluded because of a recurrence, adverse effects, or another reason. This reduction of the sample analysis may generate a bias.

The bias generated by exclusion of patients who stopped undergoing treatment or who simply failed to answer the questionnaire is obviously considerable (recurrence? toxicity? intolerance? lassitude?). These questions remain unanswered. It is therefore impossible to generalize the results of this study. Moreover, although the questionnaire completion rate was identical, it is impossible to determine whether drop-outs from the study were related to the same factors in the two groups. It would be interesting to correlate these results with those of patients who complied with treatment.

Furthermore, analysis of response included all patients who completed the baseline questionnaires and at least one other questionnaire during the study; two patients who completed only one follow-up questionnaire, one at 6 months and the other at 48 months, were therefore included in the same analysis, which prevents analysis of the time course of symptoms.

In view of the various methodologic limitations of this study, the authors' conclusions should not have been so affirmative because, according to authors "letrozole compared with placebo did not have a detrimental effect on overall quality of life after 36 months of treatment." We believe that these conclusions must be relativized and, at the present time, cannot constitute a basis for the clinical management of our patients in routine clinical practice. Consequently, despite the merit of this study concerning an essential topic, it is important to emphasize the fact that clinicians' questions still remain unanswered.

A thorough answer to these questions can probably be provided only by prospective studies, in everyday practice, taking into account patients who comply with treatment as well as those who fail to comply, while trying to optimize the quality of life questionnaire response rate.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Whelan TJ, Goss PE, Ingle JN, et al: Assessment of quality of life in MA 17: A randomized placebo controlled trial of letrozole after 5 years of tamoxifen in post-menopausal women. J Clin Oncol 23:6931-6940, 2005[Abstract/Free Full Text]

2. Osoba D, Bezjak A, Brundage M, et al: Analysis and interpretation of health-related quality of life data from clinical trials: Basic approach of the National Cancer Institute of Canada Clinical Trials Group. Eur J Cancer 41:280-287, 2005[CrossRef][Medline]

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