Abstract P1-18-30: Neoadjuvant aromatase inhibitor and pertuzumab and trastuzumab (NEOADAPT) up to one year for HR+HER2+ breast cancer: Results from a prematurely closed de-escalation study
Authors: Eugene R Ahn, Ricardo H Alvarez, Damien Hansra, Anjanette Sorensen, Jizhou Ai, Maurie Markman
Journal: Cancer Research (2020)

Abstract Background. Current standard of care for HR+HER2+ breast cancer &amp;gt;1cm per NCCN guidelines is chemotherapy with either trastuzumab(T) or trastuzumab and pertuzumab(TP) with anti-HER2 therapy continued for 1 year and anti-hormonal therapy for 5-10 years. Patients with HR+HER2+ breast cancer benefit less from chemotherapy than those with HR-HER2+ breast cancer. Recent studies show that pCR rates with aromatase inhibitor and dual-HER2 blockade for 3-6 months duration range between 21%- 33% with the highest pCR seen with 6 months. No clinical trial to date has looked at targeted therapy without chemotherapy for HR+HER2+ breast cancer up to 1 year. Methods. NEOADAPT is an IRB-approved phase II prospective single cohort study for patients with stage I-II HR+HER2+ breast cancer. Eligible pts received neoadjuvant aromatase inhibitor (and GnRH analogue or oophorectomy for premenopausal patients) and TP with q3w exams and q3mo breast MRI. Treatment may continue up to 1 year if ongoing response or radiographic CR (rCR) was observed. Surgery was allowed as soon as 3 months after the first MRI showing rCR provided the follow up MRI did not show further improvement. Primary endpoint was pCR rate defined as absence of invasive disease in the breast and lymph nodes. A Fleming two stage design was implemented with stopping rules with the null hypothesis being that the pCR rate is &amp;lt;20% versus the alternative hypothesis where the pCR rate is &amp;gt;40%. Secondary objective included median duration of treatment and exploratory analysis of correlation with Mammaprint Blueprint(MB) testing. 9 patients were enrolled before the study was prematurely closed. 3 patients who refused chemotherapy when the study was closed and were treated with the NEOADAPT protocol and fit the same inclusion/exclusion criteria are also included in this report. Results. Median age 55 (41-67); BMI 26.0 (22.2-37.6); T 2.75cm (1.3-4.8). 7 were premenopausal. 7 had disease that was HER2+ by FISH ratio &amp;gt;2.0 only (2+ IHC). All 12 patients had MB test done: 8 high risk luminal, 3 high risk HER2, and 1 low risk HER2. 5/12 patients achieved rCR, with median duration of treatment to achieve rCR in those 5 pts being 6 months (3-9). 11/12 patients have completed definitive surgery, with the outlier being a patient who refuses surgery. 4/11 patients achieved pCR all of whom received 12 months of targeted treatment before surgery. All 4 pCR patients had rCR before surgery. Of the other 3/7 pts who had rCR and not pCR, 2 had rCR at 3 months and both had surgery at 6 mo with 1.7cm and 1.5mm of residual disease seen and 1 had rCR at 6mo completed 1 yr of prescribed treatment but refused surgery. 2/12 patients were taken off study before surgery and switched to a standard of care chemotherapy regimen due to progression but remain in NED post-surgery to date. No patients to date have had local recurrence or metastatic disease. Discussion. These results from a prematurely closed study suggest as confirmed in other recent studies, that a chemotherapy-sparing endocrine and targeted neoadjuvant approach for HR+HER2+ breast cancer seems to be a feasible and reasonable option particularly for those desiring a clinically informed de-escalation to their treatment plan. Clinical trial: NCT02689921 Citation Format: Eugene R Ahn, Ricardo H Alvarez, Damien Hansra, Anjanette Sorensen, Jizhou Ai, Maurie Markman. Neoadjuvant aromatase inhibitor and pertuzumab and trastuzumab (NEOADAPT) up to one year for HR+HER2+ breast cancer: Results from a prematurely closed de-escalation study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-30.