At a median follow up of 62 months, DFS was significantly longer in early responders treated with TAC x 8 cycles compared with TAC x 6 cycles (HR, 0.78; 95% CI, 0.62 to 0.97; p=0.026). DFS was also significantly longer in early non-responders treated with TAC-NX than in those receiving TAC x 6 cycles (HR, 0.59; 95% CI, 0.49 to 0.82; p=0.001). There was no significant difference in OS observed in these two groups, though there was a trend toward improved OS in responders receiving TAC x 8 cycles compared with TAC x 6 cycles (HR, 0.76; 95% CI, 0.57 to 1.01; p=0.060).r As the sample size was calculated to provide adequate power for the primary end point, the study is underpowered for the endpoints of DFS and OS. In addition, although the groups were reasonably balanced in terms of baseline characteristics, there were fewer patients with grade 3 tumours in the non-responder group treated with TAC-NX (25%) compared with TAC x 6 cycles (36%), and this difference was statistically significant.
Rather than comparing between treatment strategies in the randomised responder vs non-responder groups, the two investigational response-guided arms (TAC x 8 and TAC-NX) were grouped and compared with the conventional therapy arms (TAC x 6). Though this grouping is somewhat counterintuitive, as the intent of the response-guided therapy in responders and non-responders is very different as is the underlying biology, the results suggest that among the hormone receptor-positive patients, DFS was comparable in patients with or without a pCR, but response-guided chemotherapy significantly prolonged DFS compared with conventional chemotherapy. For patients with hormone receptor-negative disease achieving a pCR was associated with longer DFS, but response-guided therapy did not prolong DFS.r
Disease-free and overall survival in (A, B) responding, (C, D) non-responding, and (E, F) all patients comparing response-guided with conventional chemotherapy.
© Journal of Clinical Oncology 2013