Exploring Predictive Risk Factors of Infusion Reactions with First Pertuzumab Administration in HER2-positive Breast Cancer Patients: A Single Institution Experience

Abstract

Introduction: Pertuzumab and trastuzumab are monoclonal antibodies used for treating HER2-positive breast cancer. These anti-HER2 antibodies may induce infusion reactions (IR), mainly upon first administration. We investigated factors predicting IR in the initial pertuzumab treatment for HER2-positive breast cancer.

Methods: We retrospectively reviewed the medical records of 57 patients who first received pertuzumab-containing treatment in our hospital from January 2014 to February 2021. The frequency of IR during or immediately after pertuzumab administration was examined. We also analyzed patient characteristics that may represent possible risk factors for IR.

Results: The incidence rate of IR was 44% (25/57). Red blood cell count (P < 0.001), hemoglobin (Hb) concentration (P = 0.0011), and hematocrit (P < 0.001) immediately before pertuzumab administration were significantly lower in patients with IR than in those without. In patients with IR, erythrocyte levels immediately before pertuzumab treatment were significantly lower than baseline when having received anthracycline-containing chemotherapy within three months. Logistic regression analysis showed that a decrease in Hb levels was a significant risk factor for IR (log odds ratio = -17). According to the receiver-operating characteristic analysis, a 10% decrease in Hb after anthracycline-containing treatment was the best cut-off value for predicting IR (sensitivity: 88%; specificity: 77%; area under the curve: 0.87).

Conclusions: Our study showed a higher incidence of IR after pertuzumab treatment than in clinical trials. There was a strong association between IR occurrence and erythrocyte levels lower than baseline in the group that received anthracycline-containing chemotherapy immediately before.

Keywords: HER2; breast cancer; infusion reactions; pertuzumab; risk factor.

Figure 1.

Timing of IR development. IR occurred during Tmab administration in 15 cases; just as administration was being completed or immediately after completion of Tmab administration in eight cases; about one hour after completion of Pmab-Tmab administration in two cases. The symbols indicate the symptoms experienced by patients: chills are indicated by white circles; chills and vomiting by red circles; chills, fever, and vomiting by black circles; chills, fever, and fatigue by a blue circle; fever by white squares; fever and chills by red squares; fever and vomiting by a black square; hypertension and vomiting by a blue square; nausea and vomiting by white triangles; cough, chills, fever, and vomiting by a red triangle; and vomiting, diarrhea, and fever by a black triangle. Pmab, pertuzumab; Tmab, trastuzumab.

Figure 2.

Changes in hemoglobin levels between the first dose of anthracycline and that of pertuzumab in patients who had received anthracycline treatment within the previous three months. At the point of starting AC treatment, no significant difference in Hb level was found between the groups with and without IR (median 12.6 g/dL vs. 12.4 g/dL, P = 0.36). In the group with IR, Hb significantly decreased after completing the AC treatment (median 12.6 g/dL vs. 10.5 g/dL, P < 0.001). Hb tended to decline slightly after AC treatment in the IR-free group, but not significantly (median 12.4 g/dL vs. 11.7 g/dL, P = 0.077). Bars in the boxes represent median values. AC, anthracycline-cyclophosphamide; Hb, hemoglobin; IR, infusion reaction; PER, pertuzumab.

Figure 3.

Area under the receiver-operating characteristic curve for IR prediction. When setting the cut-off line of the ratio of Hb (P) to Hb (A) at 0.90, sensitivity was 88% (15/17), and specificity was 77% (10/13) (area under the curve: 0.87; 95% CI: 0.75-1.0). AUC, area under the curve; CI, confidence interval.