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

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Lim receives research funding from Merck, Genentech, Puma Biotechnology, and Takeda. Ms Parker has stock from Amgen. Dr Arun receives research funding from Abbvie and PharmaMar and had travel expenses covered by AstraZeneca in May 2017. Dr Reuben is a consultant for Angle plc. Dr Stauder receives research funding from EMD Serono and is a member of the speakers bureau and had travel expenses covered by Varian Medical Systems. Dr Barnett was a consultant for and served as an advisory board member for Pfizer. Dr Lucci is a member of the speakers bureau for Genomic Health Inc. Dr DeSnyder receives research funding from Impedimed. Dr Varelo has received honoraria from Amgen. Dr Ueno receives research funding from Amgen, Celgene, Daiichi-Sankyo, Bayer, Genentech, Novartis, the National Institutes of Health, and Breast Cancer Research Foundation. No other disclosures are reported.

Figures

Figure.. CONSORT Flow Diagram