Competing risks of death in NCIC CTG MA.27 adjuvant exemestane versus anastrozole.
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564 Background: Our group previously examined if baseline patient/tumor characteristics, or prior treatment affected cause of death in MA.17, a placebo controlled extended adjuvant trial of the aromatase inhibitor (AI) letrozole. We now examine factor effects on all cause mortality in MA.27. Methods: MA.27 was an adjuvant phase III superiority trial of 5 yrs of exemestane vs anastrozole, in ER+ postmenopausal breast cancer accrued between 2003 and 2008; event free survival was similar. We examined by intention-to-treat, the multivariate time-to-breast cancer-specific (BrCa), cardiovascular (Cardio), and other causes (OT) of death with log-normal survival analysis adjusted by treatment and stratification factors (lymph node status, adjuvant chemotherapy, celecoxib, aspirin, and trastuzumab). We tested whether factors were associated with 1) all cause mortality, and if so, 2) cause-specific mortality. We also fit step-wise forward cause-specific adjusted models. Results: 7,576 women (median age 64.1 years; 5417 (71.5%) <70 yrs and 2159 (28.5%) >70 yrs) were enrolled and followed for a median of 4.1 yrs. The 432 deaths comprised: 187 (43.3%) BrCa, 66 (15.3%) Cardiovascular, and 179 (41.4%) OT MA.27 therapy was not associated with mortality (p=0.84). Five baseline factors were differentially associated with cause of death. Older age was associated with greater BrCa (p=0.03), Cardio (p<0.001), and OT (p<0.001) mortality. Pre-existing cardiovascular history led to worse Cardio mortality (p<0.001). Worse ECOG performance status led to worse OT death (p<0.001). T1 tumors were associated with less BrCa mortality (p<0.001). PgR+ tumors were also associated with less BrCa mortality (p<0.001). There were fewer BrCa deaths with Node –ve disease (p<0.001), ER+ tumors (p=0.001) and without adjuvant chemotherapy (p=0.005); there was worse Cardio mortality (p=0.01) with receipt of trastuzumab; worse OT (p=0.03) for non-whites, and without adjuvant radiotherapy (p=0.003). Conclusions: 56.7% of deaths in MA.27 patients were non-breast cancer related. We showed baseline patient and tumor characteristics, and prior treatment differentially affected cause of death. Clinical trial information: NCT00066573.
