Long-term cardiac outcomes of HER2+ breast cancer patients treated in the ALTTO trial

Abstract

Background: Dual HER2 blockade with trastuzumab (T) and lapatinib (L) is approved for patients (pts) with T-resistant HER2+ metastatic breast cancer, although little is known regarding the cardiotoxicity of this combination. Thus, we report cardiac data on 4,190 pts treated with 1 year of adjuvant T or concomitant T+L in ALTTO (BIG 206/N063D/EGF106708) trial. Method(s): ALTTO randomized 8,381 pts into 4 arms to investigate the benefit of L and T in early HER2+breast cancer. Our dataset consists of pts randomized to the T arm and concomitant T+L arm. Eligible pts must have had a baseline left ventricular ejection fraction (LVEF)>=50%, no serious cardiac illness and cumulative doses of doxorubicin =2 consecutive LVEF assessments of >=50% after a CE. The distribution of CEs and end-points are described by arm. A logistic regression model by arm was used to assess the odds of CEs and risk factors for its occurrence. Result(s): Pts characteristics were equally distributed among the 2 arms, except for diabetes (more common in T-arm; p=0.024). With a median follow-up of 6.5 years (range 5.6- 7.1 years), 197 (9.3%) CEs occurred in T vs 166 (7.9%) CEs in T+L arm.Median time to develop a CE was 6.4 months (range 3.6-11.7 months) in T vs 7.1 months (range 2.9-16.6 months) in T+L arm. Most CEs occurred during treatment (73.2%) and were asymptomatic (74%). Acute recovery was reached in 83.6%and 84.1%of pts in T and T+L arms, respectively. Time to recover from symptomatic CEs (T: 5.6 months; T+L: 4.2 months) was longer than for asymptomatic CEs (T: 3.1 months; T+L: 2.9 months). A 2nd LVEF drop to<50%occurred in 29.9% of pts who recovered froma CE. T was completed by 84% and 82%of pts in T and T+L arms, respectively, while L was completed by 68%of pts in T+L arm. The main reason for discontinuation of L was safety (60%), especially non-cardiac safety (82%). Five cardiac risk factors were identified (see Table). Conclusion(s): Although dual HER2 blockade does not increase the rate of cardiotoxicity compared to T alone for 1 year, identification of risk factors prior to start of therapy and close collaboration with cardiologists is essential to ensure its proper management and treatment continuity. (Table Presented) .