Abstract S3-06: A phase III trial evaluating pCR in patients with HR+, HER2-positive breast cancer treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) +/- estrogen deprivation: NRG Oncology/NSABP B-52

Background: Preclinical evidence has shown that in xenograft models with estrogen receptor (ER)+/HER2+ breast cancer, signaling through the ER pathway can be enhanced in the presence of anti-HER2 treatment and lead to treatment resistance. Concurrent targeting of ER and HER2 has led to enhanced treatment efficacy and complete tumor disappearance. We hypothesized that targeting ER with endocrine therapy concurrently with chemotherapy plus dual HER2 inhibition will not be antagonistic and can overcome ER-mediated resistance and result in higher pCR as neoadjuvant treatment of ER+/HER2+ breast cancer. NRG Oncology/NSABP B-52 is a phase III, multicenter, randomized neoadjuvant therapy trial designed to determine whether the addition of estrogen deprivation to neoadjuvant therapy consisting of docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP+Est-Dep) yields a greater rate of pCR (breast and nodes) than TCHP alone. Methods: A total of 315 patients (pts) were randomly assigned between January 15, 2014 and March 17, 2016 to receive neoadjuvant therapy consisting of TCHP with or without estrogen deprivation therapy. Pts with locally advanced, hormone receptor-positive, HER2+ invasive breast cancer with no evidence of metastatic disease were eligible. Premenopausal women randomized to estrogen deprivation therapy received ovarian function suppression with goserelin (LHRH agonist) or equivalent plus an aromatase inhibitor (AI). Postmenopausal women received an AI. The determination of pCR (breast and nodes) was defined as the absence of any invasive component in the resected breast specimen and all resected lymph nodes following completion of neoadjuvant therapy. Following the intent-to-treat principle, the difference between the rates of pCR (breast and nodes) was tested using the binomial test for the difference between two proportions. The study was designed to have a statistical power of 80% to detect an increase in the pCR rate from 45% in the TCHP alone group to 60% in the TCHP+Est-Dep group. Results: The groups were balanced, with 57% clinically node positive and 50% premenopausal. Assessments for pCR were available from 308 of 315 randomized patients. The pCR (breast and nodes) for TCHP alone and TCHP+Est-Dep were 40.9% and 46.1%, respectively (p=0.36). The pCR (breast) were 44.2% and 47.4%, respectively (p=0.57). Grade 3/4 toxicities included diarrhea (23%, Conclusion: The addition of estrogen deprivation to neoadjuvant chemotherapy is not antagonistic. It improved pCR rates numerically, but the improvement was not statistically significant. The combination did not increase toxicity and may be a reasonable approach since all patients will receive endocrine therapy after neoadjuvant therapy. Correlative science studies including evaluation of residual cancer burden (RCB) and long-term outcomes will help define the role of estrogen deprivation in the treatment of HER2+ early breast cancer. Support: U10CA180868, -180822; UG1CA189867, Genentech. Citation Format: Rimawi MF, Cecchini RS, Rastogi P, Geyer, Jr CE, Fehrenbacher L, Stella PJ, Dayao Z, Rabinovitch R, Dyar SH, Flynn PJ, Baez-Diaz L, Paik S, Swain SM, Mamounas EP, Osborne CK, Wolmark N. A phase III trial evaluating pCR in patients with HR+, HER2-positive breast cancer treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) +/- estrogen deprivation: NRG Oncology/NSABP B-52 [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 S3-06.