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

• Published in: Cancers Vol. 12; no. 12; p. 3509
• Main Authors: López-Miranda, Elena, Pérez-García, José Manuel, Di Cosimo, Serena, Brain, Etienne, Ravnik, Maja, Escrivá-de-Romaní, Santiago, Vidal, Maria, Gligorov, Joseph, Borštnar, Simona, Calabuig, Laura, Sampayo-Cordero, Miguel, Malfettone, Andrea, Llombart-Cussac, Antonio, Suter, Thomas M, Cortés, Javier
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25-11-2020; MDPI
• Subjects: Anthracycline; Antitumor activity; Breast cancer; Doxorubicin; ErbB-2 protein; Heart failure; Immunotherapy; Kinases; Liver; Metastases; Metastasis; Monoclonal antibodies; Neutropenia; Patients; Pharmacokinetics; Targeted cancer therapy; Taxanes; Thrombocytopenia; Trastuzumab; Tumors; trastuzumab emtansine; T-DM1; non-pegylated liposomal doxorubicin; HER2-positive; metastatic breast cancer
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12123509

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
) in the "3 plus 3" dose-escalation part. During expansion, they received 60 mg/m
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
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.