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Original Investigation
September 2018

Safety and Efficacy of Panitumumab Plus Neoadjuvant Chemotherapy in Patients With Primary HER2-Negative Inflammatory Breast Cancer

Author Affiliations
  • 1Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston
  • 2Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston
  • 3Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston
  • 4Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston
  • 5Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
  • 6Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston
  • 7Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston
  • 8Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston
  • 9Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston
  • 10Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston
JAMA Oncol. 2018;4(9):1207-1213. doi:10.1001/jamaoncol.2018.1436
Key Points

Question  Is the combination of the anti–epidermal growth factor receptor antibody panitumumab and neoadjuvant chemotherapy safe and effective in patients with primary human epidermal growth factor receptor 2 (HER2)-negative inflammatory breast cancer (IBC)?

Findings  In this single-arm, open-label trial, the combination of panitumumab and neoadjuvant chemotherapy produced pathologic complete response rates of 14% in patients with HER2-negative, hormone receptor–positive disease and 42% in patients with triple-negative IBC. Treatment-related hematological and dermatological toxic effects were substantial but transient, and there were no treatment-related deaths.

Meaning  The combination of panitumumab and neoadjuvant chemotherapy for primary HER2-negative IBC had significant efficacy, particularly in patients with triple-negative IBC.

Abstract

Importance  Combining conventional chemotherapy with targeted therapy has been proposed to improve the pathologic complete response (pCR) rate in patients with inflammatory breast cancer (IBC). Epidermal growth factor receptor (EGFR) expression is an independent predictor of low overall survival in patients with IBC.

Objective  To evaluate the safety and efficacy of the anti-EGFR antibody panitumumab plus neoadjuvant chemotherapy in patients with primary human epidermal growth factor receptor 2 (HER2)-negative IBC.

Design, Setting, and Participants  Women with primary HER2-negative IBC were enrolled from 2010 to 2015 and received panitumumab plus neoadjuvant chemotherapy. Median follow-up time was 19.3 months. Tumor tissues collected before and after the first dose of panitumumab were subjected to immunohistochemical staining and RNA sequencing analysis to identify biomarkers predictive of pCR.

Intervention  Patients received 1 dose of panitumumab (2.5 mg/kg) followed by 4 cycles of panitumumab (2.5 mg/kg), nab-paclitaxel (100 mg/m2), and carboplatin weekly and then 4 cycles of fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2) every 3 weeks.

Main Outcomes and Measures  The primary end point was pCR rate; the secondary end point was safety. The exploratory objective was to identify biomarkers predictive of pCR.

Results  Forty-seven patients were accrued; 7 were ineligible. The 40 enrolled women had a median age of 57 (range, 23-68) years; 29 (72%) were postmenopausal. Three patients did not complete therapy because of toxic effects (n = 2) or distant metastasis (n = 1). Nineteen patients had triple-negative and 21 had hormone receptor–positive IBC. The pCR and pCR rates were overall, 11 of 40 (28%; 95% CI, 15%-44%); triple-negative IBC, 8 of 19 (42%; 95% CI, 20%-66%); and hormone receptor–positive/HER2-negative IBC, 3 of 21 (14%; 95% CI, 3%-36%). During treatment with panitumumab, nab-paclitaxel, and carboplatin, 10 patients were hospitalized for treatment-related toxic effects, including 5 with neutropenia-related events. There were no treatment-related deaths. The most frequent nonhematologic adverse event was skin rash. Several potential predictors of pCR were identified, including pEGFR expression and COX-2 expression.

Conclusions and Relevance  This combination of panitumumab and chemotherapy showed the highest pCR rate ever reported in triple-negative IBC. A randomized phase 2 study is ongoing to determine the role of panitumumab in patients with triple-negative IBC and to further validate predictive biomarkers.

Trial Registration  ClinicalTrials.gov Identifier: NCT01036087

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