Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial.
Por:
Lopez-Miranda, E, Perez-Garcia, J, Di Cosimo, S, Brain, E, Ravnik, M, Escriva-de-Romani, S, Vidal, M, Gligorov, J, Borstnar, S, Calabuig, L, Sampayo-Cordero, M, Malfettone, A, Llombart-Cussac, A, Suter, T and Cortes, J
Publicada:
25 nov 2020
Ahead of Print:
25 nov 2020
Resumen:
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 40.0% (95%CI, 16.3-67.7) with a median duration of response of 6.9 months (95%CI, 4.8-9.1). Clinical benefit rate was 66.7% (95%CI, 38.4-88.2) and median progression-free survival was 7.2 months (95%CI, 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.
Filiaciones:
Lopez-Miranda, E:
Hosp Univ Ramon y Cajal, Dept Med Oncol, Madrid 28034, Spain
Med Scientia Innovat Res MedSIR, Dept Med, Ridgewood, NJ 07450 USA
Med Scientia Innovat Res MedSIR, Med Dept, Barcelona 08018, Spain
Perez-Garcia, J:
Med Scientia Innovat Res MedSIR, Dept Med, Ridgewood, NJ 07450 USA
Med Scientia Innovat Res MedSIR, Med Dept, Barcelona 08018, Spain
Int Breast Canc Ctr IBCC, Med Oncol Dept, Quiron Grp, Barcelona 08022, Spain
Di Cosimo, S:
Med Scientia Innovat Res MedSIR, Dept Med, Ridgewood, NJ 07450 USA
Med Scientia Innovat Res MedSIR, Med Dept, Barcelona 08018, Spain
Fdn IRCCS Ist Nazl Tumori, Dept Appl Res & Technol Dev, Biomarkers Unit, I-20100 Milan, Italy
Brain, E:
Inst Curie, Dept Med Oncol, F-92210 St Cloud, France
Ravnik, M:
Univ Med Ctr Maribor, Dept Oncol, Maribor 2000, Slovenia
Escriva-de-Romani, S:
Vall dHebron Univ Hosp, Vall dHebron Inst Oncol VHIO, Dept Med Oncol, Barcelona 08035, Spain
Vidal, M:
IDIBAPS, Dept Med Oncol, Hosp Clin, Translat Genom & Targeted Therapies Solid Tumors, Barcelona 08036, Spain
Gligorov, J:
Sorbonne Univ, Hop Tenon, AP HP, Ctr Expert Canc Sein,Inst Univ Cancerol, F-75020 Paris, France
Borstnar, S:
Inst Oncol Ljubljana, Div Med Oncol, Ljubljana 1000, Slovenia
Calabuig, L:
Med Scientia Innovat Res MedSIR, Dept Med, Ridgewood, NJ 07450 USA
Med Scientia Innovat Res MedSIR, Med Dept, Barcelona 08018, Spain
Sampayo-Cordero, M:
Med Scientia Innovat Res MedSIR, Dept Med, Ridgewood, NJ 07450 USA
Med Scientia Innovat Res MedSIR, Med Dept, Barcelona 08018, Spain
Malfettone, A:
Med Scientia Innovat Res MedSIR, Dept Med, Ridgewood, NJ 07450 USA
Med Scientia Innovat Res MedSIR, Med Dept, Barcelona 08018, Spain
:
Med Scientia Innovat Res MedSIR, Dept Med, Ridgewood, NJ 07450 USA
Med Scientia Innovat Res MedSIR, Med Dept, Barcelona 08018, Spain
Univ Catolica Valencia San Vicente Martir, Hosp Arnau Vilanova, Valencia 46015, Spain
Suter, T:
Univ Bern, Bern Univ Hosp, Dept Cardiol, Inselspital, CH-3010 Bern, Switzerland
Cortes, J:
Med Scientia Innovat Res MedSIR, Dept Med, Ridgewood, NJ 07450 USA
Med Scientia Innovat Res MedSIR, Med Dept, Barcelona 08018, Spain
Int Breast Canc Ctr IBCC, Med Oncol Dept, Quiron Grp, Barcelona 08022, Spain
Vall dHebron Inst Oncol VHIO, Dept Med Oncol, Barcelona 08035, Spain
Green Published, gold
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