Impact of treatment characteristics on response of different breast cancer subtypes: Pooled multilayer analysis of the German neoadjuvant chemotherapy trials.

Abstract

501 Background: Eight German neoadjuvant chemotherapy trials including 6,625 patients with uniform protocol and outcome definitions were conducted between 1998 and 2006 with pathological complete response (pCR) as primary endpoint. Methods: We used a more sophisticated multilevel model with random effects at the level of trials and regimens to pooled individual patient data. The model fully accounted for heterogeneity between trials in pCR. The analysis was restricted to a data set of 3,332 patients from 7 trials and 12 treatment arms with complete baseline parameters and no confounding by treatment indication based on interim response. Results: pCR was associated with an increase in cycle numbers (odds ratio [OR ] 1.2 with every two additional cycles; p = 0.009), with regimens using higher cumulative anthracycline doses (≥ 300 mg/m2 doxorubicin or ≥ 450 mg/m2 epirubicin; OR 1.6; p = 0.002), regimens with higher cumulative taxane doses (≥ 400 mg/m2 docetaxel or ≥ 700 mg/m2 paclitaxel; OR 1.6; p = 0.009), and with capecitabine containing regimens (OR 1.62; p = 0.022). Concurrent trastuzumab in patients with HER2-positive tumors increased the odds of pCR 3.2fold (p < 0.001). The association of pCR with increase in cycle numbers was more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; p for interaction = 0.046). The anthracycline dose effect was pronounced in HER2-negative tumors (OR 1.61), as compared with HER2-positive tumors (OR 0.83; p for interaction p = 0.14). There was no evidence that the effect of taxane dose (p for interaction ≥ 0.64) and the effect of capecitabine (p for interaction ≥ 0.57) varied between subtypes. PCR was not different after 4, 8 or 12 trastuzumab cycles (OR per 4 cycles increase 0.97, p = 0.87) overall or in subgroups. Conclusions: We postulate that HR-positive tumors benefit more from longer neoadjuvant treatments, HER2-negative tumors more from higher anthracycline doses, triple negative tumors from short-term higher dose taxane and anthracycline based treatment, HER2-positive tumors already from a limited number of 4 trastuzumab cycles, and all subtypes from the addition of capecitabine. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Novartis, Roche, sanofi-aventis Amgen, AstraZeneca, Novartis, Roche, sanofi-aventis AstraZeneca, Roche