Background: MARIANNE (NCT01120184) is a randomized, phase III study of T-DM1 +/- P vs HT in pts with HER2-positive advanced breast cancer (BC). Methods: Pts with previously treated inoperable locally advanced BC or untreated metastatic BC were randomized 1:1:1 to HT, T-DM1+placebo or T-DM1+P. HRQoL (FACT-B-TOI-PFB), taxane-related symptoms (FACT-Taxane), and rates of nausea, diarrhea (FACT-C items) and alopecia (APA) were assessed. PROs were completed on day 1 of the first 8 cycles; the FACT-Taxane was also completed on day 8 of the first 2 cycles. To better assess treatment impact, a more frequent assessment schedule and additional instruments (FACT-Taxane, FACT-C items) were added in a protocol amendment. Data from this more detailed assessment are presented. Time to a clinically important difference (CID) from baseline (BL; ie, an event) and event incidence were estimated. All analyses are descriptive. Results: Of 1095 pts, 498 (HT: 173, T-DM1: 171, T-DM1+P: 154) randomized after the amendment completed both BL and ≥1 follow-up visit. No clear differences in BL characteristics were found between these pts and the ITT population. Pts with a CID in HRQoL, in neurotoxicity, and specific taxane-related symptoms are shown. Conclusions: Both T-DM1 arms reported a lower incidence of and a longer time to CID in neurotoxicity, as well as less alopecia vs HT. The T-DM1 arm also reported less nausea and diarrhea than the other arms. Consistent with these and other findings in the 1L setting, baseline HRQoL, measured by the FACT-B TOI-PFB, was maintained for a longer duration in T-DM1–treated vs HT-treated pts. Clinical trial information: NCT01120184

^aCID = ≥5-point decrease from BL; ^bCID = ≥3-point increase in symptoms from BL; ^cBL = C1D1; C, cycle; D, day