Phase III, randomized study of trastuzumab emtansine (T-DM1) ± pertuzumab (P) vs trastuzumab + taxane (HT) for first-line treatment of HER2-positive MBC: Primary results from the MARIANNE study.

Breast Cancer—HER2/ER
Session Type and Session Title: 
Oral Abstract Session, Breast Cancer—HER2/ER
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr 507)
Paul Anthony Ellis, Carlos H. Barrios, Wolfgang Eiermann, Masakazu Toi, Young-Hyuck Im, Pier Franco Conte, Miguel Martin, Tadeusz Pienkowski, Xavier B. Pivot, Howard A. Burris, Alexander Strasak, Monika Patre, Edith A. Perez; Guy’s Hospital and Sarah Cannon Research Institute, London, United Kingdom; PUCRS School of Medicine, Porto Alegre, Brazil; Interdisciplinary Oncology Center, Munich, Germany; Graduate School of Medicine, Kyoto University, Kyoto, Japan; Samsung Medical Center, Seoul, South Korea; Department of Surgery, Oncology and Gastroenterology, University of Padova and Istituto Oncologico Veneto, Padova, Italy; Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain; Postgraduate Medical Education Center, Warsaw, Poland; University Hospital Jean Minjoz, Besançon, France; Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Nashville, TN; F. Hoffmann-La Roche Ltd, Basel, Switzerland; F. Hoffmann-La Roche Ltd., Basel, Switzerland; Mayo Clinic, Jacksonville, FL

Abstract Disclosures


Background: In phase II and III studies, treatment with T-DM1 or with P + H + docetaxel has shown statistically significant increases in progression-free survival (PFS) and overall survival (OS) vs control regimens in patients with HER2-positive MBC. The combination of T-DM1 + P resulted in synergistic inhibition of tumor cell line proliferation in vitro. This and preliminary data from a phase II clinical trial provided the rationale for further study. Methods: In MARIANNE (NCT01120184), patients with centrally assessed HER2-positive (IHC3+ or ISH+) progressive/recurrent locally advanced BC or previously untreated MBC with a ≥ 6-month interval since treatment in the (neo)adjuvant setting with taxanes or vinca alkaloids were randomized 1:1:1 to HT (docetaxel or paclitaxel + H), T-DM1 (T-DM1 + placebo, hereafter T-DM1), or T-DM1 + P, at standard doses. The primary end point was PFS assessed by independent review. Comparisons between HT and T-DM1 or T-DM1 + P were considered separately. PFS was tested first for non-inferiority and for superiority only if non-inferiority was achieved. Results: At the clinical cutoff date, September 16, 2014, 365 patients had been randomized to HT, 367 to T-DM1, and 363 to T-DM1 + P. In each arm, approximately 31% of patients had prior (neo)adjuvant treatment with HER2-directed therapy. Approximately 37% overall had de novo disease. The study met the PFS non-inferiority end point, but not the superiority end point. OS was similar across treatment arms. Conclusions: These data demonstrate non-inferiority in PFS between T-DM1–containing arms and control. T-DM1–containing regimens were associated with a different toxicity profile than the control regimen. Clinical trial information: NCT01120184

OutcomeHTT-DM1T-DM1 + P
Median follow-up, mo34.834.934.7
Median PFS, mo13.714.115.2
HR [97.5% CI]-0.91 [0.73–1.13],
p = 0.31 vs HT
0.87 [0.69–1.08],
p = 0.14 vs HT
0.91 [0.73–1.13],
p = 0.31 vs T-DM1
ORR, %67.959.764.2
Median duration of
response, mo
Grade 3−5 AEs, %54.145.446.2
Most common grade 3−5 AEs, %
Febrile neutropenia6.500
AST increased0.36.63.0