Abstract P4-21-05: Neoadjuvant non-pegylated liposomal doxorubicin plus paclitaxel, trastuzumab and pertuzumab in patients with HER2+ breast cancer – Final results of the SOLTI OPTI-HER HEART study
Authors: Gavilá J , Perez-Garcia J , Calvo I , Ciruelos E , Muñoz M , Virizuela JA , Ruiz I , Andrés R , Morales S , Perelló A , Sánchez P , Garcia-Saenz JA , Quero Guillen JC , González-Santiago S , Garau Llinas I , González-Martín A , Cantos Sánchez de Ibargüen B , Zaragoza K , de la Peña L , Llombart-Cussac A , Oliveira M 
Published: March 2017

Abstract
INTRODUCTION
Targeting HER2 by dual blockade with trastuzumab (T) and pertuzumab (P) in a taxane-based regimen is an active neoadjuvant treatment (NAT) of HER2+ early breast cancer (EBC). Addition of an anthracycline could further enhance this response, but potential cardiac toxicity is a concern. The Opti-HER HEART trial (NCT01669239) aims to optimize neoadjuvant treatment while minimizing cardiac risk, by combining T+P with a taxane and non-pegylated liposomal doxorubicin (NPLD).
MATERIAL AND METHODS
Phase II open-label, single-arm study of six 21-day cycles of NPLD (50mg/m2 D1), paclitaxel (80mg/m2 D1,8,15), T (4mg/kg C1D1, followed by 2mg/kg weekly), and P (840mg C1D1, followed by 420mg C2-6D1) as NAT for patients (pts) with stage II-IIIB HER2+ BC. Primary objective was to evaluate cardiac safety of the combination, measured by the incidence of type A (symptomatic congestive heart failure ) or type B [asymptomatic reduction of Left Ventricular Ejection Fraction (LVEF) value: ≥10% absolute decrease and LVEF&lt;50%, LVEF&lt;40% or any absolute decrease ≥20%] events, during NAT. Eighty-three pts were required to reject with 80% confidence the null hypothesis that the combination increases the incidence of cardiac events above the historical control of 18% (3% type A; 15% type B).
RESULTS
Between June 2013 and January 2015, 83 pts with HER2+ EBC (stage II 78%, stage III 22%) and adequate cardiac function (LVEF≥55%) were enrolled. Mean age was 50 years, N+ 47%, hormone receptor (HR) positive 71% and median baseline LVEF 66%. Eighty-five percent of pts completed 6 cycles of NAT, whereas 15% discontinued NAT due to toxicity. Adverse events (AEs) leading to dose adjustments/temporary interruptions and discontinuation of at least 1 drug occurred in 70% and 21% of pts, respectively. Primary objective was met with an incidence of cardiac events during NAT of 4% (95%CI 1-10, 3pts, all type B). Cardiac events until study completion (1 year) were 8% (all type B). All (but 2 cases with no follow-up data) were reversible and only 1 pt presented an asymptomatic LVEF&lt;40%. Neutropenia (45%) was the most frequent hematological toxicity (G3/4 34%; febrile neutropenia 6%), less frequent in the 71% of pts that received primary G-CSF prophylaxis (G3/4 25% vs. 67%). Common non-hematological toxicities were diarrhea (74%; G3 7%), asthenia (78%; G3 11%) and neurotoxicity (52%; G3/4 10%). Pathological complete response (pCR) in breast+axilla (ypT0/is ypN0) was 60% (87% in HR-) and 69% in breast (91% in HR-).
TOTALHR-HR+% ypT0/is (95% CI)69 (58-79)91 (72-99)61 (47-74)% ypT0/is ypN0 (95% CI)60 (46-71)87 (66-97)50 (36-64)
CONCLUSIONS
The neoadjuvant combination of T+P, paclitaxel and NPLD does not increase the risk for cardiac events in HER2+ BC pts. Since cardiac toxicities may present later, long-term cardiac monitoring is essential. Efficacy in terms of pCR was remarkable, being higher to historical values of combinations with dual anti-HER2 blockade and one of the highest reported among HR-HER2+ BC. This regimen administered with primary G-CSF prophylaxis and cardiac function monitoring may be an effective and secure option for early and locally advanced HER2+ pts with good cardiac function.
Citation Format: Gavilá J, Perez-Garcia J, Calvo I, Ciruelos E, Muñoz M, Virizuela JA, Ruiz I, Andrés R, Morales S, Perelló A, Sánchez P, Garcia-Saenz JA, Quero Guillen JC, González-Santiago S, Garau Llinas I, González-Martín A, Cantos Sánchez de Ibargüen B, Zaragoza K, de la Peña L, Llombart-Cussac A, Oliveira M. Neoadjuvant non-pegylated liposomal doxorubicin plus paclitaxel, trastuzumab and pertuzumab in patients with HER2+ breast cancer – Final results of the SOLTI OPTI-HER HEART study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-05.