Abstract PS10-42: Clinical outcomes with neoadjuvant chemotherapy plus dual anti-HER2 therapy in patients with operable/locally advanced breast cancer: Single institution experience

Background: Pertuzumab, a monoclonal antibody targeting subdomain II of HER2 and blocking dimerization, was approved by the FDA in 2013 as neoadjuvant therapy in combination with trastuzumab + chemotherapy for HER2+ locally advanced or early-stage breast cancer patients (pts). TCHP (Docetaxel/Carboplatin/Trastuzumab/Pertuzumab) is a popular, non-anthracycline neoadjuvant therapy. In the TRYPHAENA trial, pathologic complete response (pCR) rate was 63.6% with 6 cycles of neoadjuvant TCHP (47.5% in ER+/PR+ and 81.1% in ER-/PR- tumors). We previously reported (SABCS 2015) our institutional experience with neoadjuvant TCHP in 75 pts with operable/locally advanced HER2+ breast cancer (10/2013 - 12/2015). Now we report our updated experience of 230 pts (10/2013 - 12/2019) with neoadjuvant chemotherapy + dual anti-HER2 therapy. Patients & Methods: Medical record search identified HER2+ pts (T1c-T3/N0-3 or Tany/N1-3) treated with neoadjuvant chemotherapy + dual anti-HER2 therapy from 10/2013 to 12/2019. Collected information included pt and tumor characteristics at diagnosis, details of neoadjuvant therapy, clinical, radiologic, & pathologic assessment of tumor response, type of breast and axillary nodal surgery, and long-term disease outcomes. Results: 230 pts (229 female, 1 male) met the inclusion criteria; median age: 52 yrs (range 25-79); Clinical stage: I (2%), II (78%) , III (20%); ER+ and/or PR+ 70% ; ER-/PR- 30%. 228 pts received TCHP and 2 pts AC then THP. 170 pts (74%) received 6 cycles of TCHP without dose reduction; 49 pts (21%) received 6 cycles, but with dose reduction (most commonly due to diarrhea, nausea, neutropenia, and anemia); 11 pts (5%) received Of the 230 pts who underwent breast surgery (1 had no breast primary at presentation), 86 pts (38%) had breast conserving surgery, 19 (8%) unilateral mastectomy, and 124 (54%) bilateral mastectomy. Axillary assessment was by SLNB in 75% and ALND in 25% (with/without SLNB). Among 138 pts with cN0 and axillary assessment, 124 had SLNB (4 had + nodes), 14 had ALND (11 had + nodes). Among 91 pts with cN1-3, 47 had SLNB (1 had + nodes) and 44 had ALND (27 had + nodes). Overall pCR rate (ypT0/Tis, ypN0) was 59%. pCR rate was 50% for ER+ and/or PR+, and 79% for ER-/PR-. pCR by Stage: I (50%), II (60%), III (55%). At median follow-up of 2.9 years, 221 pts (96%) were alive with no evidence of disease; 8 pts (3.5%) have experienced recurrence (6 distant, 1 locoregional, 1 unknown site), and 1 pt died after developing AML as the only event. The table below presents details on the 8 pts who suffered recurrence: 4 had clinical stage II disease, and 4 clinical stage III. All pts had hormone receptor + tumors at diagnosis. 7 of 8 pts (88%) with recurrence did not have pCR at surgery. Most common sites of distant metastases as first event were liver and bone. Of the 8 pts with recurrence, 6 are alive with disease (median follow-up 2.8 years). There was 1 death due to disease progression, and 1 pt was lost to follow-up. Conclusions: Our updated results continue to demonstrate the clinical safety and efficacy of neoadjuvant therapy with TCHP for operable/locally advanced HER2+ breast cancer. Our pCR rates are similar to those observed in the TRYPHAENA trial. Longer follow-up is required to evaluate the long-term clinical outcomes with this regimen. Citation Format: Nirja Shah, Nikita Shah, Said Baidas, Ana Cuesta-Fernandez, Marc Demers, Maria Demori, Tomas Dvorak, Rachel Eisenberg, Terrence Gross, Danielle Henry, Michael Kahky, Patrick Kelly, Swathy Kolli, Regan Rostorfer, Jeffrey Smith, Cameron Swanick, Eleftherios Mamounas. Clinical outcomes with neoadjuvant chemotherapy plus dual anti-HER2 therapy in patients with operable/locally advanced breast cancer: Single institution experience [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-42.