Defining clinical benefit in postmenopausal patients with breast cancer under second-line endocrine treatment: does quality of life matter?

Abstract

In endocrine therapy trials in advanced breast cancer, patients with response (complete response/partial response [CR/PR]) and patients with stable disease for at least 6 months (SD(6m)) have shown similar survival and therefore are often defined as a population with clinical benefit (patients with CR/PR or SD(6m)). We evaluated the impact of response and/or clinical benefit on quality of life (QL) in postmenopausal patients under second-line endocrine treatment after failure of tamoxifen. One hundred twenty-eight of 177 eligible patients of a randomized trial (Swiss Group for Clinical Cancer Research 20/90) receiving either formestane (250 mg intramuscularly biweekly) or megestrol acetate (160 mg orally daily) were analyzed. The baseline characteristics (with the exception of site of metastases) were balanced among patients with CR/PR, SD(6m), and progressive disease (PD). Patients completed QL indicators at baseline and at 1, 3, 5, 7, 9, and 11 months. Responders were separately compared with nonresponders (patients with SD(6m) or PD) and with patients with SD(6m), and patients with clinical benefit were compared with patients with PD by analysis of covariance with adjustment for baseline scores. Overall, 88% (557 of 634) of expected QL forms were received. In the comparison of responders versus patients with both SD(6m) and PD, responders indicated better physical well-being (P =. 004) and mood (P =.02) at month 3. Compared only with patients with SD(6m), responders showed no significant difference in baseline QL and time to treatment failure (328.5 v 340 days). While under treatment, responders reported significantly better physical well-being (months 3 to 11), mood (months 5 to 11), coping (months 5 to 9), and appetite (months 7 to 11) and less dizziness (month 9) than patients with SD(6m). The changes between baseline and months 5 and 7, respectively, indicated improvement in responders but heterogeneous patterns in patients with SD(6m). Although the CR/PR and SD(6m) groups had similar times to treatment failure, patients with CR/PR reported better QL, suggesting more beneficial response to second-line endocrine treatment. Patients' subjective perspective should be taken into account in this mainly palliative setting. Future trials should be designed so that the CR/PR and SD(6m) groups are investigated separately.