Abstract P5-16-28: A single-institution clinical experience with neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP): A safety and efficacy analysis
Authors: Tariq R , Ajaz B , Shah N , Mamounas E , Moroose R 
Published: March 2017

Background: Pertuzumab, a monoclonal antibody targeting subdomain II of HER2 and blocking dimerization , was approved by the FDA in 2013 for use in combination with trastuzumab and docetaxel as neoadjuvant therapy for pts with HER2+, locally advanced, inflammatory or early-stage breast cancer (&gt;2cm and/or node-positive). This accelerated approval was based on results from the NeoSphere and the TRYPHAENA trials. In NeoSphere, pathologic complete response in the breast and nodes [pCR] was 39.3% after 4 cycles of neoadjuvant pertuzumab/trastuzumab/docetaxel. In TRYPHAENA, pCR was 63.6% among 76 patients treated with 6 cycles of neoadjuvant TCHP(47.5% in pts with ER+and/or PR+/HER2+ tumors and 81.1% in those with ER-/PR-/HER2+ tumors). Aside from TRYPHAENA, we have limited information on clinical outcomes, with neoadjuvant TCHP. Here we report our institutional experience at UF Health Cancer Center, Orlando (UFHCC) with Neoadjuvant TCHP in patients with operable or locally advanced breast cancer.

Patients and Methods: After IRB approval, electronic medical record search was performed in order to identify HER2+ patients with tumors T2-T4/N0-3 or Tany/N1-3, treated with neoadjuvant TCHP between 10/13 and 5/16. Information from chart review included patient and tumor characteristics at the time of diagnosis , details of neoadjuvant chemotherapy plus anti-HER2 therapy, clinical, radiologic and pathologic assessment of tumor response to neoadjuvant TCHP, type of breast and axillary nodal surgery, surgical outcomes as well as disease outcomes.

Results: 76 patients (75 female, 1 male) met the inclusion criteria; median age: 52 yrs; 83% of pts presented with clinical stage II and 17% with clinical stage III; 62% were ER+ and/or PR+ and 38% were ER-/PR-negative. 49 patients received all planned 6 cycles without dose reduction. The remaining 27 patients required dose reduction due to rash, diarrhea, nausea, vomiting, neuropathy or neutropenia; 5 patients requested dose reduction due to poor quality of life and fatigue; 2 patients required dose delay due to asymptomatic cardio-toxicity with ≥ 10% drop in EF. None had symptomatic CHF; 37% of patients underwent breast conserving surgery, 7% unilateral mastectomy and 55% bilateral mastectomy. Surgical lymph node assessment was performed after neoadjuvant chemotherapy and included sentinel lymph node biopsy (SLNB) in 74%, axillary dissection (ALND) in 8% or both in 18% of pts. Overall pCR rate (ypT0/is, ypN0) was 63.2%. pCR rate was 53.1% in pts with ER+ and/or PR+ tumors and 79.3% in those with ER-/PR- tumors. pCR by stage was 61% for Stage IIA, 65% for Stage IIB, 67% for Stage IIIA and 71% for Stage IIIC. Toxicity profile was consistent with what has been observed in the TRYPHAENA trial with fatigue, nausea, vomiting and neuropathy being the more commonly noted grade 3/4 toxicities. With median follow up of 18 months, all patients are disease-free with no documented recurrences observed.

Conclusion: Our clinical experience with neoadjuvant TCHP confirms the efficacy and safety data from the TRYPHAENA trial in a single-institution, tertiary care center setting.

Citation Format: Tariq R, Ajaz B, Shah N, Mamounas E, Moroose R. A single-institution clinical experience with neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP): A safety and efficacy analysis [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 P5-16-28.