Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial.

Elena López-Miranda, José Manuel Pérez-García, Serena Di Cosimo, Etienne Brain, Maja Ravnik, Santiago Escrivá-de-Romaní, Maria Vidal, Joseph Gligorov, Simona Borštnar, Laura Calabuig, Miguel Sampayo-Cordero, Andrea Malfettone, Antonio Llombart-Cussac, Thomas M. Suter, Javier Cortés

Research output: Contribution to journalArticlepeer-review

Abstract

The paper assesses the dose-limiting toxicities and the maximum tolerated dose (MTD) of trastuzumab emtansine (T-DM1) combined with non-pegylated liposomal doxorubicin (NPLD) in HER2-positive (HER2+) metastatic breast cancer (MBC). This single-arm, open-label, phase Ib trial (NCT02562378) enrolled anthracycline-naïve HER2+ MBC patients who had progressed on trastuzumab and taxanes. Patients received a maximum of 6 cycles of NPLD intravenously (IV) at various dose levels (45, 50, and 60 mg/m(2)) in the "3 plus 3" dose-escalation part. During expansion, they received 60 mg/m(2) of NPLD every 3 weeks (Q3W) plus standard doses of T-DM1. The MTD was T-DM1 3.6 mg/kg plus NPLD 60 mg/m(2) administered IV Q3W. No clinically relevant worsening of cardiac function was observed. Among all evaluable patients, the overall response rate was 40.095 16.3-67.7) with a median duration of response of 6.9 months (95 4.8-9.1). Clinical benefit rate was 66.795 38.4-88.2) and median progression-free survival was 7.2 months (95 4.5-9.6). No significant influence of NPLD on T-DM1 pharmacokinetics was observed. The addition of NPLD to T-DM1 is feasible but does not seem to improve the antitumor efficacy of T-DM1 in HER2+ MBC patients.
Original languageEnglish
JournalCancers
Volume12
Issue number12
DOIs
Publication statusPublished - Nov 1 2020

Keywords

  • *HER2-positive
  • *metastatic breast cancer
  • *non-pegylated liposomal doxorubicin
  • *T-DM1
  • *trastuzumab emtansine

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