Perez EA, Barrios C, Eiermann W, et al. - Researchers report final outcomes, including overall survival (OS), safety, additional patient-reported outcomes and data from biomarker analyses, from the phase 3 MARIANNE trial, wherein noninferior progression-free survival and better tolerability of trastuzumab emtansine (T-DM1) with or without pertuzumab was shown, compared with trastuzumab plus a taxane (HT) for the first-line treatment of human epidermal growth factor receptor 2 (HER2)–positive advanced breast cancer. Overall 1095 cases with no prior therapy for advanced disease were included. HT, T-DM1 plus a placebo (hereafter T-DM1), or T-DM1 plus pertuzumab (T-DM1+pertuzumab) had been randomly received by these patients. Longer median OS was achieved with T-DM1 (64.4 months) and T-DM1+pertuzumab (not reached) vs HT (56.3 months) among patients with objective tumor response. With HT (55.8%), a greater incidence of grade 3 or higher adverse events was reported, as compared with T-DM1 (47.1%) or T-DM1+pertuzumab (48.6%). Overall, first-line treatment with T-DM1 in patients with HER2-positive metastatic breast cancer who are deemed unsuitable for taxane-based therapy was supported.