Acceptable Cardiac Safety of Ado-Trastuzumab Emtansine After Anthracycline-Based Chemotherapy in Early-Stage HER2-Positive Breast Cancer
In a study reported in the Journal of Clinical Oncology, Krop et al found that ado-trastuzumab emtansine (Kadcyla) had an acceptable cardiac safety profile when used after anthracycline-based (neo)adjuvant therapy in women with early-stage HER2-positive breast cancer.
Study Details
In the study, 153 patients with a pretreatment left ventricular ejection fraction > 55% received (neo)adjuvant doxorubicin-cyclophosphamide for four cycles or fluorouracil, epirubicin, and cyclophosphamide for three or four cycles followed by ado-trastuzumab emtansine 3.6 mg/kg every 3 weeks for four cycles. Patients could then receive three or four cycles of docetaxel with or without trastuzumab (Herceptin). Ado-trastuzumab emtasine treatment was then resumed with optional sequential or concurrent radiotherapy for up to 1 year (17 cycles).
The coprimary endpoints were safety and rate of prespecified cardiac events within the first 12 weeks of ado-trastuzumab emtansine treatment. The prespecified cardiac events were death resulting from a cardiac cause or severe congestive heart failure (New York Heart Association class III or IV) accompanied by a decrease in left ventricular ejection fraction of ≥ 10% from baseline to < 50%.
Cardiac Events
Median follow-up was 24.6 months. No prespecified cardiac events or symptomatic congestive heart failure was reported. Asymptomatic left ventricular ejection fraction declines of ≥ 10% from baseline to < 50% occurred in four patients (2.7%), with ado-trastuzumab emtansine being discontinued in one (0.7%). Other ado-trastuzumab emtansine–related cardiac events occurred in five patients (3.4%), including grade 4 atrial fibrillation in one (0.7%), grade 3 tricuspid valve incompetence in one (0.7%), grade 1 palpitations in four (2.7%), and grade 2 supraventricular extrasystole in one (0.7%).
Other Adverse Events
Of 148 patients who received at least one cycle of ado-trastuzumab emtansine, 82% completed the planned 1 year of treatment. The most common adverse events of any grade during ado-trastuzumab emtansine treatment were nausea (38%), headache (37%), epistaxis (32%), and asthenia (30%). Grade 3 adverse events occurred in 38.5% of patients, with the most common being thrombocytopenia (8.1%), increased aspartate transaminase (7.4%), and increased alanine transaminase (7.4%). Grade 4 adverse events occurred in 2.7% of patients (febrile neutropenia and pancytopenia, atrial fibrillation, thrombocytopenia, and hypokalemia).
At least 95% of the planned radiotherapy dose was completed with a delay ≤ 5 days in 95% of 38 patients receiving concurrent radiotherapy and 96% of 77 receiving sequential radiotherapy.
The investigators concluded: “Use of [ado-trastuzumab emtansine] for approximately 1 year after anthracycline-based chemotherapy was feasible and generally well tolerated by patients with HER2-positive [early-stage breast cancer], providing support for phase III trials of [ado-trastuzumab emtansine] in this setting.”
Ian E. Krop, MD, PhD, of Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.
The study was supported by Genentech, a member of the Roche group. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
