General and Supportive CareAssessment of quality of life in advanced breast cancer. An overview of randomized phase III trials
Introduction
With nearly 1.3 million new cases and almost half a million deaths annually, breast cancer is among the most important health problems, especially in developed nations.1 Breast cancer mortality in the western world has decreased over the last decade as a consequence of the wider use of screening mammography and more effective adjuvant therapy.2 Even though hormone therapy, chemotherapy, and HER-2 targeted therapy are able to decrease the risk of disease relapse in early-stage breast cancer, treatment failure occurs in a substantial number of patients, and the median survival for metastatic breast cancer remains in the range of mere 2 to 3 years.3, 4, 5 The management of advanced breast cancer is thus a major clinical challenge for medical oncologists. Since cure for this disease remains elusive for most patients, the chief therapeutic goal is palliation aiming at prolongation of survival with good quality of life and symptom control.6
During the past decades, health care has progressively shifted its focus solely from the disease process to include patient well-being and health-related quality of life (HRQOL) as important outcomes,7 particularly in medical oncology.8 The use of HRQOL data to help guide selection of optimal treatment is best addressed in the context of randomized controlled trials.9 The primary objective of randomized controlled trials in medical oncology is generally related to the efficacy of interventions. Nevertheless, more attention has recently been paid to improving the way patients live during cancer treatment.10, 11 As a result, HRQOL assessment has become an important secondary objective in cancer clinical trials, including those in breast cancer.9, 12, 13, 14
Although HRQOL assessment has many potential utilities and implications for clinical practice and research, the role of HRQOL data to help the selection of therapy for breast cancer is still unclear. A few years ago, Goodwin et al.9 examined 20 trials in advanced breast cancer that were published between 1987 and 2001 and in which HRQOL had been assessed. These authors found that HRQOL assessment in those studies provided little additional information beyond that obtained from traditional medical outcomes, leading them to state that “the routine use of HRQOL measurement in randomized drug trials in metastatic breast cancer may not be warranted unless one or more of the agents being tested has very modest or differing toxicities that could have an effect on HRQOL”. Even though HRQOL parameters are often used as end points in phase III trials of systemic therapy for advanced breast cancer, the extent to which this has been done in recent studies, and the frequency and correlates of significant gains in HRQOL, have not been systematically assessed. In the current study, our objective was to analyze HRQOL results in phase III trials reported over the past 12 years, in an attempt to evaluate the contemporary role for HRQOL assessment in advanced breast cancer.
Section snippets
Search strategy
In previous studies, we have looked at various aspects concerning the use of end points in the recent literature on advanced breast cancer.5, 15 In brief, our trial selection criteria consisted in using PubMed and the medical subject headings “breast neoplasms” and “drug therapy” to search for the main paper reporting the efficacy results of phase III trials on systemic antineoplastic therapies published between January 1, 1998, and July 15, 2009 in 11 leading journals (Annals of Oncology,
Characteristics of the phase III trials
The search identified 87 phase III trials that were eligible for analysis (a complete list of the trials is available upon request). Such trials enrolled a total of 33,669 evaluable patients in 192 trial arms. Two of these arms, one in each trial, consisted of the use of placebo or best supportive care alone as maintenance after patients had achieved disease stability or a partial response to first-line therapy. Except for 10 trials with three arms, two factorial trials with four arms each, and
Discussion
The current study shows that HRQOL end points have been used in approximately 40% of contemporary phase III trials in advanced breast cancer. In most of the trials in which such end points were used, formal HRQOL statistical comparisons between groups were undertaken. However, significant differences between groups were found in only four of 31 trials (13%). Of note, in one of these studies HRQOL assessment was part of a composite end point in which ‘gain from treatment’ was evaluated.37 We
Disclosures
The authors have declared no conflicts of interest.
Acknowledgment
The authors wish to thank Prof. Neil Aaronson for his helpful discussions of the manuscript.
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