Safety and efficacy of panitumumab plus neoadjuvant chemotherapy in patients with primary HER2-negative inflammatory breast cancer

Naoko Matsuda, Xiaoping Wang, Bora Lim, Savitri Krishnamurthy, Ricardo H. Alvarez, Jie S. Willey, Charla A. Parker, Juhee Song, Yu Shen, Jianhua Hu, Wenhui Wu, Nan Li, Gildy V. Babiera, James L. Murray, Banu K. Arun, Abenaa M. Brewster, James M. Reuben, Michael C. Stauder, Chad M. Barnett, Wendy A. WoodwardH. T. Carisa Le-Petross, Anthony Lucci, Sarah M. DeSnyder, Debu Tripathy, Vicente Valero, Naoto T. Ueno

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

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 IBCwere 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 (2.5mg/kg) followed by 4 cycles of panitumumab (2.5mg/kg), nab-paclitaxel (100mg/m2), and carboplatin weekly and then 4 cycles of fluorouracil (500mg/m2), epirubicin (100mg/m2), and cyclophosphamide (500mg/m2) every 3 weeks. MAIN OUTCOMES AND MEASURES The primary end pointwas 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.

Original languageEnglish (US)
Pages (from-to)1207-1213
Number of pages7
JournalJAMA Oncology
Volume4
Issue number9
DOIs
StatePublished - Sep 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

MD Anderson CCSG core facilities

  • Biostatistics Resource Group

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