Author/Editor		López-Miranda, Elena; Pérez-García, José Manuel; Cosimo, Serena Di; Brain, Etienne; Ravnik-Oblak, Maja; Vidal, Maria; Gligorov, Joseph; Borštnar, Simona; Calabuig, Laura; Malfettone, Andrea
Title		Trastuzumab emtansine plus non-pegylated liposomal doxorubicin in HER2-positive metastatic breast cancer (Thelma)
Type		članek
Vol. and No.		Letnik 12, št. 12
Publication year		2020
Volume		str. 3509-1-3509-14
ISSN		2072-6694 - Cancers
Language		eng
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/m2) in the %3 plus 3% dose-escalation part. During expansion, they received 60 mg/m2 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/m2 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 e%cacy of T-DM1 in HER2+ MBC patients.
Keywords		trastuzumab rak dojke HER2-pozitivni metastatski rak trastuzumab breast cancer HER2-positive breast cancer