Background The phase 3 BOLERO-2 study randomized 724 patients with hormone-receptor–positive (HR+) advanced breast cancer and recurrence or progression during/after nonsteroidal aromatase inhibitor therapy to everolimus (EVE) plus exemestane (EXE) or EXE and placebo (PBO). Interim analysis after 12 months' median follow up demonstrated that EVE + EXE significantly improved progression-free survival (PFS) vs EXE + PBO, with a higher rate of grade 3/4 adverse events but no deterioration in QOL. We report here on additional post hoc analyses of patient-reported QOL. Methods Using the EORTC QLQ-C30 questionnaire and QLQ-BR23 module, QOL was assessed at baseline and every 6 weeks thereafter until progression or discontinuation. The QLQ-C30 consists of 30 items combined into 15 subscales, including Global Health Status (GHS). The BR23 consists of 23 items specific to breast cancer combined into symptom and functioning subscales, including breast symptom (BS) and arm symptom (AS) scales. Average difference in change from baseline between treatment groups was evaluated using linear mixed models with several adjustment covariates. Sensitivity analysis was conducted using pattern-mixture models to examine the effect of study dropout on or before week 24. Treatments were compared using differences of least squares mean (LSM) changes from baseline at each timepoint and overall. Results Linear mixed models indicated no statistically significant overall difference between EVE + EXE and EXE + PBO for GHS (LSM difference = –2.0; 95% CI = –4.8, 0.9), breast symptoms (LSM difference = 0.3; 95% CI = –2.8, 2.4), or arm symptoms (LSM difference = –0.2; 95% CI = –2.8, 2.4). Pattern-mixture models indicated that patients who dropped out early had worsening QOL over time in both treatment arms; EVE + EXE patients who did not drop out early had stable QOL, whereas EXE + PBO was associated with worsening QOL over time. Conclusions These additional analyses from the BOLERO-2 study confirm that compared with EXE alone, EVE + EXE improved PFS without adversely impacting QOL in patients with HR+ advanced breast cancer progressing despite nonsteroidal aromatase inhibitors.
