T-DM1 versus pertuzumab, trastuzumab and a taxane as first-line therapy of early-relapsed HER2-positive metastatic breast cancer: an Italian multicenter observational study

Background: The current standard first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive (þ) metastatic breast cancer is the combination of pertuzumab, trastuzumab and a taxane (P þ T þ taxane), while standard second-line is ado-trastuzumab-emtansine (T-DM1). The registration trial of pertuzumab, however, did not include earlyrelapsing patients, defined as patients experiencing tumor relapse 12 months from the end of (neo)adjuvant anti- HER2 therapy. Conversely, the pivotal trial of T-DM1 included some patients relapsing 6 months after the end of (neo)adjuvant trastuzumab. Thus, a proportion of early-relapsing patients are currently eligible to receive T-DM1 as first-line treatment. Nevertheless, no direct comparison exists between the two regimens in this clinical setting. Patients and methods: We retrospectively compared T-DM1 versus P þ T þ taxane as first-line treatment in two cohorts of early-relapsing patients in an Italian ‘real-world’ setting, involving 14 public health care institutions. The primary endpoint was progression-free survival. Secondary endpoints included patients’ characterization, overall survival and post-progression survival. Univariate and multivariate analyses were carried out. All tests were twosided and a P 0.05 was considered statistically significant. Results: Among 1252 screened patients, 75 met the inclusion criteria. Forty-four (58.7%) received P þ T þ taxane and 31 (41.3%) received T-DM1. The two cohorts showed similar characteristics of aggressiveness and no significant differences in treatment history. T-DM1, compared with P þ T þ taxane was associated with worse progression-free survival (adjusted hazard ratio: 2.26, 95% confidence interval: 1.13-4.52, P ¼ 0.021) and overall survival (adjusted hazard ratio: 3.95, 95% confidence interval: 1.38-11.32, P ¼ 0.010), irrespective of previous (neo)adjuvant treatment, age, hormone receptors status, time-to-relapse (6 months or within 6-12 months) and presence of visceral/brain metastases. No differences were observed in post-progression survival (P ¼ 0.095). Conclusions: Our study suggests superiority for P þ T þ taxane over T-DM1 as up-front treatment of early-relapsing HER2þ metastatic breast cancer, which merits further assessment in larger and prospective trials.