Abstract OT3-01-07: Phase II study of trastuzumab and pertuzumab alone and in combination with hormonal therapy or chemotherapy with eribulin in women aged ≥60 with HER2/neu overexpressed locally advanced and/or metastatic breast cancer
Authors: Rosenblatt PY , Kesmodel SD , Bellavance E , Nichols EM , Feigenberg SJ , Tait N , Lewis J , Sivisailam SS , Couzi R , Goloubeva O , Tkaczuk KHR 
Published: May 2016

Abstract
Her2 overexpression is both a predictive and prognostic marker with tumors overexpressing Her2 having an aggressive natural history, but also responding to targeted therapy. The standard of care for Her2 positive metastatic cancer is docetaxel paired with combined antibody therapy of pertuzumab (P) and trastuzumab (T). Older patients are known to have more difficulty tolerating traditional cytotoxic chemotherapy. Neoadjuvant studies have shown a proportion of patients have pathologic complete responses (pCR) with dual Her2 targeted therapy without chemotherapy. The NEOSPHERE trial demonstrated at 17% pCR after 3 cycles of T+P. The Translational Breast Cancer Research Consortium has shown 12-28% pCR with the combination of estrogen deprivation, trastuzumab, and lapatinib (TBCRC 006 and 023). We have designed a phase II study of T+P alone and then in combination with hormonal or chemotherapy after progression in women age ≥ 60 with Her2 overexpressed locally advanced or metastatic breast cancer (BC). As a primary endpoint, this study seeks to evaluate the overall response rate (ORR) of dual Her2 targeted therapy with T+P without chemotherapy in older patients with locally advanced or metastatic Her2 positive BC (cohort 1). At progression,depending on tumor characteristics and disease status, chemotherapy with eribulin or hormone therapy with anastrozole plus fulvestrant will be added (cohort 2 – A and B). ORR for cohorts 1, 2A and 2B will be determined. Secondary end points will evaluate clinical benefit, progression free survival, overall survival, tolerability, safety, and quality of life. Translational studies involving circulating tumor cells identified through OncoCEE – Biocept system and glycoprotein 88 expression will be performed. Eligibility includes patients' age ≥60 with locally advanced or metastatic Her2 positive BC treated with 0-3 lines of chemotherapy. Patients must have an ejection fraction &gt;50% and meet set hematologic and metabolic lab criteria. Her2 status is per ASCO/ACP guidelines. Excluded patients include patients with active brain metastasis, second malignancies, anticancer treatment &lt;3 weeks prior to the start of therapy. Patients must have not received pertuzumab, eribulin, anastrozole, or fulvestrant in the metastatic setting. A true ORR of 40% will be considered active. The study was designed assuming 25% of patients initially respond to T+P and 75% progress to cohort 2. With a type I error rate of 0.05 and power of 0.90, 40 patients will need to enroll in order to have 30 patients in cohort 2 (15 per arm). Data will be analyzed after eight patients are enrolled. If there are no responders in cohort 1 and 2, the accrual will be stopped and declared inefficient. After 15 patients are enrolled, if no more than 3 of the 15 respond, the therapy will be considered not promising and halted. Currently there are two patients enrolled at the University of Maryland. We are in negotiations to expand to additional sites. Questions can be directed to prosenblatt@umm.edu.
Citation Format: Rosenblatt PY, Kesmodel SD, Bellavance E, Nichols EM, Feigenberg SJ, Tait N, Lewis J, Sivisailam SS, Couzi R, Goloubeva O, Tkaczuk KHR. Phase II study of trastuzumab and pertuzumab alone and in combination with hormonal therapy or chemotherapy with eribulin in women aged ≥60 with HER2/neu overexpressed locally advanced and/or metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-01-07.