Abstract PS10-42: Clinical outcomes with neoadjuvant chemotherapy plus dual anti-HER2 therapy in patients with operable/locally advanced breast cancer: Single institution experience
Authors: Shah Nirja , Shah Nikita , Baidas Said , Cuesta-Fernandez Ana , Demers Marc , Demori Maria , Dvorak Tomas , Eisenberg Rachel , Gross Terrence , Henry Danielle , Kahky Michael , Kelly Patrick , Kolli Swathy , Rostorfer Regan , Smith Jeffrey , Swanick Cameron , Mamounas Eleftherios 
Published: February 2021

Abstract
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 &lt; 6 cycles (7 of those also needed dose reduction). Mean left ventricular ejection fraction was 62.0% pre-treatment, and 60.9% post-treatment.
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.
Recurrence DataPatient NumberAge at DiagnosisDate of DiagnosisHormone Receptor at DiagnosisClinical Stage at DiagnosisType of Breast SurgerypCRPathologic Stage at SurgeryDate of RecurrenceTime to Metastases (Years)Site of Recurrence16511/19/14PositivecT2N1 (IIB)Left MastectomyYesypT0N0 (0)4/6/172.4Liver, Bone2366/15/15PositivecT2N0 (IIA)Bilateral MastectomyNoypT3N0 (IIB)3/19/182.8Liver3546/29/15PositivecT2N3 (IIIC)Left MastectomyNoypT1bN1a (IIA)10/2/194.3Bone4577/1/15PositivecT2N3 (IIIC)Left LumpectomyNoypT1cN1a (IIA)2/4/193.6Bone, Soft Tissue5568/20/15PositivecT2N0 (IIA)Left LumpectomyNoypT1aN0 (IA)6/28/182.8Lymph Node6264/29/16PositivecT4N0 (IIIB)Bilateral MastectomyNoypT2N1 (IIB)12/13/171.6Liver7539/27/16PositivecT3N3 (IIIC)Bilateral MastectomyNoypT3N3 (IIIC)Not KnownNot KnownNot Known8319/3/17PositivecT2N1 (IIB)Bilateral MastectomyNo (clinical progression)ypT3N2a (IIIC)6/25/180.8Lungs
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.