Abstract CT029: Chemotherapy-free neoadjuvant regimen with durvalumab, trastuzumab and pertuzumab (DTP) in HER2-enriched early breast cancer: A prospective, open-label phase II trial
Authors: Guan Jian , Sun Kai , Jain Dharamvir , Mathur Sunil , Mai Hanh , Niravath Polly , Chang Jenny 
Published: April 2024

Abstract
Background: High risk HER2-positive early breast cancer (EBC) patients are traditionally treated with neoadjuvant chemotherapy in combination with HER2-directed therapy. De-escalation approaches are being studied as benefits of chemotherapy in the HER2-enriched subset of EBC, but they have been inconclusive thus far. Preclinical studies suggest synergistic effect of immune checkpoint blockade (ICB) and HER2-directed therapy. This study hypothesizes that biologically directed HER-2 targeted therapy with Trastuzumab (T) and Pertuzumab (P) together with ICB (Durvalumab, D) will obviate the need of chemotherapy in HER2-enriched EBC patients.
Methods: In this single arm, open-label phase II study, previously untreated, stage I-III, ER/PR negative, HER2-enriched breast cancer (BluePrint®, Agendia) patients were treated with D (1120mg IV, q3w), T (8mg/kg IV loading dose, 6 mg/kg IV q3w), and P (840 mg IV loading dose, 420 mg IV q3w) for 6 cycles. Response was assessed at end of 6 cycles with breast MRI and possible biopsy if residual disease was present. Responders (MRI and/or biopsy negative for residual cancer) proceeded to surgery, while patients with biopsy-proven residual disease were offered salvage standard chemotherapy (TCHP) before surgery. Primary end-point was pathological response rate defined as residual cancer burden (RCB)-0 and RCB-1. Patients who achieved RCB 0/1 received adjuvant DTP for 1 year.
Results: A total of 51 patients were screened; 39 patients have been enrolled and received at least one cycle of treatment. Of these, 35 patients are evaluable for pathologic response, and 2 patients are still receiving treatment. One patient died of unrelated myocardial infarction, and one patient was lost to follow-up. The median age was 55 years (range 29-85). Thirty-one (79.5%) patients were white; 4 (10.3%) African American, and 4 (10.3%) Asian. Twenty-nine (74.3%) patients had &gt;=T2 tumors; 21 (53.8%) patients had N1/N2/N3 disease. Six patients (15.3%) had biopsy-proven residual disease after DTP therapy, and they received salvage standard neoadjuvant TCHP chemotherapy. The combination was well tolerated; 5 (18.8%) patients had G3-4 adverse events. Twenty-seven of thirty-five patients (77.1%) had pathologic RCB 0/1 (RCB0, 20/35; RCB1 7/35), of whom only 3 patients had received salvage chemotherapy. Correlative studies, including tumor-infiltrating lymphocytes, immune-related gene signatures and PD-L1 expression are underway.
Conclusions: Chemotherapy-free neoadjuvant regimen with DTP in HER2-enriched EBC showed high pathologic response rates comparable to that with chemotherapy. This DTP regimen may provide an effective, relatively non-toxic, and biologically driven alternative to standard of care chemotherapy in this HER2-enriched subset of EBC.
Citation Format: Jian Guan, Kai Sun, Dharamvir Jain, Sunil Mathur, Hanh Mai, Polly Niravath, Jenny Chang. Chemotherapy-free neoadjuvant regimen with durvalumab, trastuzumab and pertuzumab (DTP) in HER2-enriched early breast cancer: A prospective, open-label phase II trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT029.