Characterization of infections and hypogammaglobulinemia treated with the combination of pertuzumab and trastuzumab

Abstract

Purpose We update a patient series that reported a high incidence of infection with Gram-positive cocci in women treated with the combination of pertuzumab and trastuzumab and further characterize this clinical problem. Patients Treating physicians and advanced practice partners identified women who developed infections while on treatment with pertuzumab and trastuzumab alone or in combination with chemotherapy and enrolled them onto this registry trial. Results Between March, 2014 and May, 2017, 48 patients with HER2-positive breast cancers were reported to have 59 individual infections. The median age was 48 years. Twenty-four patients received neoadjuvant therapy, 17 were treated for metastatic disease, and 7 were treated in the adjuvant setting. Pertuzumab and trastuzumab were combined with carboplatin and docetaxel in 24 (49%) patients, docetaxel in 10 (21%), nab-paclitaxel in 12 (24%), and without other agents in 2 (4%). Granulocyte growth factors were administered in 24 (49%) patients and no patients were documented to be neutropenic. Folliculitis developed in 25 (52%) patients and was counted as a single infection. Abscesses developed at a number of sites in 24 (49%) patients, including a septic knee requiring total knee replacement. Paronychia occurred in 7 (15%) patients, and 5 (10%) developed cellulitis. When cultures were obtained, Gram-positive cocci were consistently identified. Hypogammaglobulinemia was documented in 14 (36%) of the 33 patients tested. Conclusions Our data continue to support an increased risk of infections with Gram-positive cocci as a potentially serious adverse event in women treated with pertuzumab and trastuzumab.

Surgical Intervention for Paronychia Induced by Targeted Anticancer Therapies

“…Epidermal growth factor receptor/HER2 dual kinase inhibitors 6,7 Poziotinib Lapatinib Afatinib HER2 monoclonal antibodies 7,8 Pertuzumab Trastuzumab mTOR inhibitors 3 Sirolimus Everolimus Temsirolimus MEK inhibitors 3 Trametinib Selumetinib Cobimetinib…”

“…Drug-induced paronychia is a common toxicity in targeted anticancer therapies such as epidermal growth factor receptor inhibitors (EGFRis), mitogen-activated protein kinase kinase (MEK) inhibitors, mechanistic target of rapamycin (mTOR) inhibitors, and phosphatidylinositol-3-kinase inhibitors (PI3Kis) (Table 1). 2–10 Epidermal growth factor receptor inhibitors inhibit typical pathways involved in epithelial maturation leading to instability and inflammation of periungual tissue. 11 Based on a previous meta-analysis, EGFRi treatment led to nail toxicities in 17.2% of patients.…”