Long-term cardiac outcomes of patients with HER2-positive breast cancer treated in the adjuvant lapatinib and/or trastuzumab Treatment Optimization Trial
Daniel Eiger, Noam Pondé, Dominique Agbor‐Tarh, Alvaro Moreno‐Aspitia, Martine Piccart, Florentine Hilbers, Olena Werner, Saranya Chumsri, Amylou C. Dueck, Judith R. Kroep, Henry Gómez, István Láng, Richard J. Rodeheffer, Michael S. Ewer, Thomas Suter, Evandro de Azambuja
Abstract
Abstract Background Cardiotoxicity is the most significant adverse event associated with trastuzumab (T), the main component of HER2-positive breast cancer (BC) treatment. Less is known about the cardiotoxicity of dual HER2 blockade with T plus lapatinib (L), although this regimen is used in the metastatic setting. Methods This is a sub-analysis of the ALTTO trial comparing adjuvant treatment options for patients with early HER2-positive BC. Patients randomised to either T or concomitant T + L were eligible. Cardiac events (CEs) rates were compared according to treatment arm. Results With 6.9 years of median follow-up (FU) and 4190 patients, CE were observed in 363 (8.6%): 166 (7.9%) of patient in T + L arm vs. 197 (9.3%) in T arm (OR = 0.85 [95% CI, 0.68–1.05]). During anti-HER2 treatment 270 CE (6.4%) occurred while 93 (2.2%) were during FU (median time to onset = 6.6 months [IQR = 3.4–11.7]). While 265 CEs were asymptomatic (73%), 94 were symptomatic (26%) and four were cardiac deaths (1%). Recovery was observed in 301 cases (83.8%). Identified cardiac risk factors were: baseline LVEF < 55% (vs > 64%, OR 3.1 [95% CI 1.54–6.25]), diabetes mellitus (OR 1.85 [95% CI 1.25–2.75]), BMI > 30 kg/m 2 (vs < 25 mg/kg 2 , OR 2.21 [95% CI 1.40–3.49]), cumulative dose of doxorubicin ≥240 mg/m 2 (OR 1.36 [95% CI 1.01–1.82]) and of epirubicin≥ 480 mg/m 2 (OR 2.33 [95% CI 1.55–3.51]). Conclusions Dual HER2 blockade with T + L is a safe regimen from a cardiac perspective, but cardiac-focused history for proper patient selection is crucial. Trial registration number ClinicalTrials.gov Identifier: NCT00490139 (registration date: 22/06/2007); EudraCT Number: 2006–000562–36 (registration date: 04/05/2007); Sponsor Protocol Number: BIG2–06 /EGF106708/N063D.