Abstract P6-15-11: Weekly paclitaxel, pertuzumab and trastuzumab (TPH) neoadjuvant therapy for HER2 positive inflammatory breast cancer
Authors: Overmoyer B , Regan M , Hu J , Nakhlis F , Dominici L , Lin NU , Freedman R , Morganstern DE , Partridge AH , Schlosnagle EJ , Hirshfield-Bartek J , Bellon J , Morikawa A , Harrison BT , Winer E 
Published: February 2018

Abstract
Background: Inflammatory breast cancer (IBC) is inoperable at presentation, thus neoadjuvant systemic therapy (NAS) is the primary treatment for this aggressive disease. Due to its rarity, patients (pts) with IBC are incorporated into NAS clinical trials for locally advanced breast cancer, making it difficult to extrapolate efficacy specifically for pts with IBC. A commonly used regimen for the treatment of HER2+ IBC includes docetaxel, carboplatin, pertuzumab (P) and trastuzumab (H), yet only 6% of pts enrolled in the clinical trial for this regimen had IBC. We sought to examine the efficacy of maximizing anti-HER2 therapy combined with minimal chemotherapy using the THP regimen specifically for pts with HER2+ IBC.
Methods: Pts with newly diagnosed HER2+ IBC received NAS with 16 weeks (wks) of paclitaxel (T) 80mg/m2/wk, H (2mg/kg/wk) and P(420mg/kg/3wk) followed by modified radical mastectomy (MRM) on a phase II prospective study. All pts had 2 research breast biopsies (rbx) for correlative assays prior to and 1 wk after the P (840mg/kg) and H (4 mg/kg) loading dose. Pts who achieved a pCR (pathologic complete response) could opt out of adjuvant doxorubicin (A) 60 mg/m2 + cyclophosphamide (C) 600mg/m2 x 4; pts with residual disease received AC. All pts received post-mastectomy radiation and maintenance P (420mg) + H (6mg/kg) every 3 wks x 12. Adjuvant endocrine therapy was given per standard of care. Primary objective was pCR rate in the breast and axillary lymph nodes. Residual Cancer Burden (RCB) was assessed. Based upon a Simon two-stage design, this regimen would be declared worthy of further study if &gt;7/27 pCR were observed (15% vs 40%; target α=0.039 power=0.90). The study was closed after 23/27 pts were enrolled due to slow accrual.
Results: 20 pts were enrolled as of 12/2016, 18 completed NAS and MRM. All but 1 had stage III disease at presentation. 1 pt was lost to follow-up; 1 developed CNS metastasis during NAS and did not undergo MRM. The mean age was 49 years, 10 pts had ER/PR negative disease. 15 pts completed 16 wks of T, 4 had 15 wks and 1 had 13 wks. During NAS, there was no grade (gd) 4 toxicity; 6 episodes of gd 3 toxicity (2 related to treatment-diarrhea); and no gd 3 cardiac events. In the intent to treat analysis, 10/20 pts achieved pCR (50%; 90% CI 30-70%) and 6 had RCB-1 (30%). 5 pts with RCB-1 response had &lt;5 mm residual disease; 1 had lymph node involvement. Of those proceeding to MRM, pCR rate was 56% (10/18). 6/10 opted out of AC. Treatment and follow-up for clinical outcomes continue. Biologic correlatives investigating genomic profiling and patterns of HER2 resistance are being performed on rbx, residual disease and cfDNA.
Conclusion: THP x 16wks is tolerable and effective NAS for HER2+ IBC, resulting in a high pCR rate with minimal toxicity. This study of NAS explored the benefit of maximizing HER2-directed therapy and minimizing chemotherapy and its associated toxicity. It has achieved its primary endpoint and will be used as the backbone NAS for HER2+ IBC, with future studies building upon this regimen. The result of this trial supports the benefit of clinical trials designed specifically for pts with IBC. Clinical trial information: NCT01796197.
Citation Format: Overmoyer B, Regan M, Hu J, Nakhlis F, Dominici L, Lin NU, Freedman R, Morganstern DE, Partridge AH, Schlosnagle EJ, Hirshfield-Bartek J, Bellon J, Morikawa A, Harrison BT, Winer E. Weekly paclitaxel, pertuzumab and trastuzumab (TPH) neoadjuvant therapy for HER2 positive inflammatory breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-11.