Phase III, Randomized Study of First-Line Trastuzumab Emtansine (T-DM1) ± Pertuzumab (P) Vs. Trastuzumab + Taxane (HT) Treatment of HER2-positive MBC: Final Overall Survival (OS) and Safety from MARIANNE.

1003 Background: In MARIANNE (NCT01120184), patients with HER2-positive advanced breast cancer were randomized to trastuzumab + docetaxel or paclitaxel (HT; n=365), T-DM1 + placebo (T-DM1; n=367), or T-DM1 + P (T-DM1 + P; n=363) as first-line therapy. In the primary analysis, T-DM1–based treatment exhibited noninferior, but not superior, progression-free survival relative to HT (Perez EA, et al. J Clin Oncol 2016). OS was similar between treatments in the first interim analysis. Here we report OS from the final descriptive analysis. Methods: Enrolled patients had centrally assessed HER2-positive (IHC3+ or ISH+) progressive/recurrent locally advanced breast cancer or previously untreated MBC with a ≥6-month interval since (neo)adjuvant treatment with taxanes or vinca alkaloids. Results: At the clinical cutoff date of May 15, 2016, median follow-up was 54 months and 512 patients had died. Median OS was 50.9, 53.7, and 51.8 months with HT, T-DM1, and T-DM1 + P, respectively (Table). A sensitivity analysis in which HT-treated patients who received T-DM1 and/or P after disease progression (n=85) were censored prior to treatment switch found similar results. There were numerically fewer grade ≥3 adverse events (AEs) with T-DM1. Conclusions: With this longer follow-up, the T-DM1 safety profile was consistent with the primary analysis and prior experience. While OS was similar across treatment arms, a median OS of 53.7 months and fewer grade ≥3 AEs (vs other arms) supports T-DM1 as an effective and tolerable alternative first-line treatment for HER2-positive MBC patients. Clinical trial information: NCT01120184. [Table: see text]