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 antiHER2 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.