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Risk of rash with the anti-HER2 dimerization antibody pertuzumab: a meta-analysis

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Abstract

Pertuzumab is a novel humanized monoclonal antibody that blocks human epidermal growth factor receptor 2 (HER2) dimerization. It was recently approved by the US FDA for use in combination with trastuzumab and docetaxel for patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Rash is inconsistently reported as a common adverse event in most clinical trials of pertuzumab, at varying incidences. In this study, we have investigated the overall incidence and risk of rash with pertuzumab. Relevant studies were identified from the PubMed database (1966–2012), abstracts presented at the American Society of Clinical Oncology annual conference (2004–2011), and Web of Science database (1998–2012). Eligible studies were prospective phase II–III clinical trials using pertuzumab in cancer patients. Incidence, relative risk (RR), and 95 % confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Data from a total of 1,726 patients (pertuzumab, n = 1,157; controls, n = 569) with breast, ovarian, and prostate cancers from eight clinical trials were included for analysis. The incidence of all-grade and high-grade rash with pertuzumab were 24.6 % (95 % CI 19.3–30.8 %) and 1.1 % (95 % CI 0.5–2.2 %), respectively. The risk varied with tumor types, as patients with prostate cancer had a lower incidence of rash (13.2 %; 95 % CI 8.0–21.1 %) than those with breast, ovarian, fallopian tube, and peritoneal cancer (P = 0.001). Overall, pertuzumab significantly increased the risk of rash in comparison with controls (RR 1.53; 95 % CI 1.12–2.09; P = 0.007). Pertuzumab is associated with a significant risk of rash, and the incidence varies among different tumor types. Prevention, early recognition, and appropriate treatment of this rash may lead to improvement in patient quality of life, adherence to therapy, and possibly optimize clinical outcomes.

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Acknowledgments

Dr. Drucker received funding from the Canadian Dermatology Foundation.

Conflict of interest

This study was not sponsored. Drs. Drucker and Wu declare that they have no conflicts of interest. Dr. Dang receives research funding from Roche and Genentech and has consulted for them. She has not received honoraria). Dr. Lacouture consults for Genentech and Roche.

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Authors and Affiliations

  1. Division of Dermatology, Department of Medicine, University of Toronto, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    Aaron M. Drucker

  2. Division of Hematology and Medical Oncology, Stony Brook University Cancer Center, 3 Edmund D Pellegrino Road, Stony Brook, NY, 11794, USA

    Shenhong Wu

  3. Breast Cancer Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 300 East 66th Street, New York, NY, 10065, USA

    Chau T. Dang

  4. Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Rockefeller Outpatient Pavilion, Suite 228, 160 East 53rd Street, New York, NY, 10022, USA

    Aaron M. Drucker & Mario E. Lacouture

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  1. Aaron M. Drucker
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  2. Shenhong Wu
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  3. Chau T. Dang
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  4. Mario E. Lacouture
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Correspondence to Mario E. Lacouture.

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Drucker, A.M., Wu, S., Dang, C.T. et al. Risk of rash with the anti-HER2 dimerization antibody pertuzumab: a meta-analysis. Breast Cancer Res Treat 135, 347–354 (2012). https://doi.org/10.1007/s10549-012-2157-7

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  • DOI: https://doi.org/10.1007/s10549-012-2157-7

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