Abstract OT1-03-04: A phase II study of neoadjuvant aromatase inhibitor with pertuzumab and trastuzumab for patients with ER+HER2+ stage I-II breast cancer (NEOADAPT)
Authors: Ahn ER , Alvarez R , Maurie M 
Published: February 2018

Abstract
Background. Recent clinical trial results indicate that it is more appropriate than ever to conduct de-escalation clinical trials looking at less chemotherapy for patients with relatively early stage HER2+ breast cancer, particularly those with so called triple positive breast cancer (ER+PR+HER2+, or TPBC). TBCRC 006 showed that if hormone therapy is added to dual-HER2 blockade (lapatinib and trastuzumab) pathological complete response rate (pCR) can increase to 21% with another 22% having low residual disease (&lt;1cm) with only 12 weeks of neoadjuvant therapy. After CLEOPATRA showed unprecedented improvement in OS comparing docetaxel trastuzumab and pertuzumab versus docetaxel and trastuzumab (15.7 mo median OS difference), we designed NEOADAPT to test the hypothesis that a flexible duration of neoadjuvant treatment based on clinical and radiographic response with an aromatase inhibitor coupled with pertuzumab and trastuzumab would have a &gt;40% pCR rate. The potential impact of this trial is to provide more treatment options for women with early stage TPBC in a current environment when more than 40% of such patients are currently getting chemotherapy.
Trial Design. This single arm prospective cohort study is IRB approved and currently enrolling (NCT02689921). Intervention will be neoadjuvant aromatase inhibitor +/- LHRH agonist or oophorectomy if premenopausal with trastuzumab and pertuzumab in standard q 3-week dosing schedules. Duration of treatment will be determined by clinical exam, q 3mo dynamic breast MRI but no longer than 1 year maximum before surgery. Study ends upon definitive surgery. Duration of treatment will be 3 months after last radiographic CR seen on MRI barring progression or patient/physician choice.
Eligibility Criteria. Patients with stage I-II biopsy confirmed invasive breast cancer that is ER/PR+ and HER2+ by latest ASCO guidelines. Multifocal breast cancer is allowed on the provision that all lesions are biopsied and confirmed to also be TPBC and felt by the pathologist to be the same tumor. Age &gt;18 yrs, ECOG PS 0-2, LVEF &gt;50% at baseline. Rest of inclusion and exclusion criteria are typical for most studies in this setting.
Specific Aims. The primary endpoint is to document pCR rate. Secondary endpoints are to conduct an exploratory analysis of whether Mammaprint can identify patients who are more likely to obtain pCR or not and to describe sensitivity and specificity of breast MRI in predicting pCR.
Statistical Design. To identify a hypothesized pCR rate of &gt;40% with 80% power, 32 patients will be enrolled. The Fleming two stage design will be implemented with stopping rules with the first stage of interim analysis done when the first 15 evaluable patients have surgical results. Further details will be provided in poster.
Present accrual and target accrual. At time of abstract submission 5 of 32 patients have been enrolled and the study is currently available at 2 Cancer Treatment Centers of America sites, Midwestern and Southeastern Regional Medical Center. Plan is to open the study at all 5 CTCA sites before end of 2017.
Contact information for those specifically interested in this trial. Principal investigator Eugene Ahn MD eugene.ahn@ctca-hope.com.
Citation Format: Ahn ER, Alvarez R, Maurie M. A phase II study of neoadjuvant aromatase inhibitor with pertuzumab and trastuzumab for patients with ER+HER2+ stage I-II breast cancer (NEOADAPT) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-03-04.