In both the early-stage and metastatic breast cancer settings, diarrhea was frequently associated with pertuzumab-containing regimens, but did not often lead to dose delays or treatment discontinuation, according to a study published in the journal Annals of Oncology.1
Pertuzumab targets the extracellular dimerization domains of the human epidermal growth factor receptor 2 protein (HER2), thereby blocking ligand-dependent heterodimerization of HER2 with other HER family members, including EGFR, HER3, and HER4. As such, pertuzumab could result in adverse events similar to those observed with EGFR antagonists, such as diarrhea.
Therefore, researchers sought to determine the incidence and severity of diarrhea observed with pertuzumab in the CLEOPATRA, NeoSphere, and TRYPHAENA trials. For the study, investigators analyzed data from 1443 patients with metastatic breast cancer included in the CLEOPATRA trial and 639 patients with early-stage breast cancer included in the NeoSphere and TRYPHAENA studies.
Results showed that the incidence of all-grade diarrhea across studies was generally greater for pertuzumab-based treatment, ranging from 28% to 72%. Most cases of diarrhea were grade 1 (21% to 54%) and grade 2 (8% to 37%). Grade 3 cases of diarrhea ranged from 0% to 12% and 0% of patients reported grade 4 diarrhea.
Researchers found that the incidence of diarrhea was highest during the first cycle of pertuzumab-containing therapy, with incidences decreasing during subsequent cycles. Dose delays or treatment discontinuations ranged from 0% to 8%.
Among patients with metastatic breast cancer, Asian patients treated with pertuzumab appeared to experience all-grade diarrhea more frequently than white patients (74% vs 63%). In addition, patients age 65 years and older treated with pertuzumab had a higher incidence of grade 3 diarrhea than those younger than 65 years (19% vs 8%).
Investigators also evaluated the incidence of febrile neutropenia concurrent with diarrhea and the effect of pre-existing gastrointestinal comorbidities. They observed no relationship between pre-existing gastrointestinal comorbidities and diarrhea, and overlap between diarrhea and febrile neutropenia was infrequent, ranging from 0% to 11%.
1. Swain SM, Schneeweiss A, Gianni L, et al. Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab. Ann Oncol. doi: 10.1093/annonc/mdw695. [Epub ahead of print]