Abstract P4-15-21: Skin infections associated with the addition of pertuzumab to trastuzumab-containing chemotherapy
Authors: Mortimer Joanne E , Yuan Yuan , Stewart Daphne , Chung Samuel , Kruper Laura , Wong Louise C , Mendelsohn Mary , Behrendt Carolyn , Dadwal Sanjeet , Tegtmeier Bernard 
Published: May 2015

Abstract
Objectives: The addition of pertuzumab, to trastuzumab-based chemotherapy is currently considered first-line therapy for locally advanced and metastatic disease HER2 positive breast cancer and has also been suggested for use in the adjuvant setting. Over the past 12 months, we have observed an increase in the incidence of severe skin infections in patients receiving chemotherapy with pertuzumab and trastuzumab. We report the natural history of what we believe is a previously unrecognized toxicity of these regimens. Methods: Shortly after the FDA approval of pertuzumab, our clinical team appreciated an increase in invasive skin infections. We discussed this concern and identified new cases at our weekly research meeting, keeping a log of cases as they were identified. Infection control reviewed the individual patient and hospital data during this time period. Results: Eleven women were identified to have severe skin and/or nail infections; 6 after cycle 1; 2 after cycle 2, 1 after cycle 3 and 2 after cycle 6. The median age was 51 (Range 46-64); 9 received pertuzumab, trastuzumab, carboplatin, and docetaxel (PTCH) and 2 pertuzumab, trastuzumab, and docetaxel. Folliculitis of the scalp, abdomen, and/or buttocks were observed in 4 patients. Abscesses were observed in 5 patients, 4 of whom required incision and drainage. Severe paronychial infections involving one to 16 digits were observed in 3 (including one who also had folliculitis). 1 pt required surgical removal of 2 nails. Quantitative immunoglobulins were found to be low in 2 of 8 women tested; 1 patient had a total protein of 4.7 but did not have an assessment of quantitative immunoglobulins. All patients were initially treated with oral antibiotics, but 3 required hospitalization. Cultures were obtained on 6 patients, Staph aureus was identified in 2 and methicillin resistant Staph (MRSA) in 4. All patients resolved their infections and 9 of 10 were able to complete six cycles of chemotherapy. Infection control could identify no increase in Staph infections at our institution. Patients were treated at different locations and received different lot numbers of drug.
Conclusions: We believe this is the first report of a substantial incidence of invasive skin and nail infections with the addition of pertuzumab to trastuzumab-based regimens not reported in the product label. Low levels of quantitative immunoglobulin in select patients suggest a possible mechanism.
Citation Format: Joanne E Mortimer, Yuan Yuan, Daphne Stewart, Samuel Chung, Laura Kruper, Louise C Wong, Mary Mendelsohn, Carolyn Behrendt, Sanjeet Dadwal, Bernard Tegtmeier. Skin infections associated with the addition of pertuzumab to trastuzumab-containing chemotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-15-21.