Intravenous Cetirizine Prevents Infusion Reactions From Paclitaxel in Breast Cancer, Other Tumors

Intravenous (IV) cetirizine (Quzyttir) showed comparable efficacy to IV diphenhydramine for the prevention of infusion reactions (IRs) in patients with cancer who are undergoing treatment with an anti-CD20 antibody or paclitaxel, according to results from a prospective, phase 2 trial (NCT04189588) that were presented during the 38th Annual Miami Breast Cancer Conference®.

Findings showed that the IR rate in patients who received IV cetirizine was 11.8% (n = 2/17) compared with 17.6% (n = 3/17) in those who received IV diphenhydramine. One of 3 patients with breast cancer experienced an IR.

“This was the first prospective, randomized, controlled trial evaluating IV antihistamine pretreatment for the prevention of IRs,” Jarrod P. Holmes, MD, FACP, medical oncology at St. Joseph Health Medical Group, and coinvestigators noted in the poster presented at the meeting. “IV cetirizine was associated with less sedation, less time in the treatment center, and fewer treatment-related [adverse effects (AEs)] than IV diphenhydramine.”

Pretreatment with antihistamine for drug-induced hypersensitivity is recommended to be used with other chemotherapies, including paclitaxel, for patients with breast cancer. IV cetirizine is a second-generation IV antihistamine and has been shown to treat patients with acute urticaria with outcomes comparable to that of IV diphenhydramine but with fewer toxicities. The study authors suggested that IV cetirizine may also show promise as a pretreatment of IRs.

In the prospective, double-blind, randomized, controlled, phase 2 trial, investigators sought to compare the incidence of IRs to treatment with an anti-CD20 antibody, such as rituximab (Rituxan), or paclitaxel, following pretreatment with IV cetirizine (n = 17) or IV diphenhydramine (n = 17) during infusion.

IRs were defined as flushing, itching, alterations in heart rate and blood pressure, dyspnea, chest discomfort, acute back or abdominal pain, fever, shaking, chills, nausea, vomiting, diarrhea, skin rashes, throat tightening, hypoxia, seizures, syncope, or dizziness.

Pretreatment was given with a single IV dose of 10-mg cetirizine or IV diphenhydramine at 50 mg in 34 patients who were being treated with paclitaxel, rituximab or a rituximab biosimilar, or obinutuzumab (Gazyva) at the first cycle or retreatment after 6 months or in patients with persistent IRs while on maintenance or retreatment.

To be eligible for enrollment, patients had to be 18 years or older, could be male or female, and required treatment premedication with an antihistamine for hypersensitivity IRs linked with rituximab or paclitaxel. Those who had a high risk of developing tumor lysis syndrome, may have contraindications with an antihistamine, had received any antihistamine within 24 hours prior to receiving the study drug regardless of the administration route, and who had received an H2 antagonist in the prior 4 hours before receiving study drug, were excluded.

The primary end point of the trial was the incidence of IRs following pretreatment; the key secondary end point was sedation score due to IV antihistamines. Sedation was assessed by health care providers as well as patients on a scale of 0 to 4 (0 = none; 4 = extremely severe/asleep). Time to readiness for discharge served as another efficacy end point, the investigators noted in the poster.

The patient population comprised those with both hematologic and solid tumors, including breast cancer, and were enrolled between March 25, 2020 and November 23, 2020. An addition of patients receiving paclitaxel was added to the protocol in amendment 2 on August 10, 2020. Twenty-five patients had received an anti-CD20 agent and 9 had been given paclitaxel; those who had received the anti-CD20 drug had hematologic malignancies or immune disorders, while those who had paclitaxel had solid tumors, 3 of whom had breast cancer.

The median age of the participants was 66.0 years (range, 36-87), 35.3% were female, and most were White (76.5%) and not Hispanic or Latino (82.4%).

Additional data showed that the mean sedation scores in the IV cetirizine arm was 0.5 (0.72), 0.6 (0.61), and 0.1 (0.33) vs 1.3 (1.26), 0.9 (1.14), and 0.4 (0.71) in the IV diphenhydramine arm at 1 hour, 2 hours, and at discharge, respectively, as rated by the patients enrolled on the trial. Moreover, these data were similar with the health care provider­–rated sedation scores.

The median time for readiness for discharge was 24 minutes less with IV cetirizine compared with IV diphenhydramine, at 4 hours and 18 minutes and 4 hours and 42 minutes, respectively.

Regarding safety, fewer patients experienced treatment-related AEs with IV cetirizine (n = 2) vs IV diphenhydramine (n = 4). Treatment-emergent AEs (TEAEs) occurred in 8 and 9 patients, respectively. In the IV cetirizine arm, these TEAEs were mild in 2 patients, moderate in 4, severe in 1, and life-threatening in 1; none were fatal. In the IV diphenhydramine arm, 3 cases were mild, 5 were moderate, and 1 was fatal; no severe or life-threatening TEAEs were reported.

Overall, 2 and 4 TEAEs were possibly related to study treatment; there were 0 AEs that led to discontinuation of study treatment in either arm.

The TRAEs in the IV cetirizine arm included insomnia, dyspepsia, and malaise; in the IV diphenhydramine arm, these effects were diarrhea, injection site pain, headache, somnolence, dizziness, and lightheadedness.

In the poster, investigators noted that study limitations include the small sample size without formal statistics.

“However, the results of key secondary end points of sedation score, time to discharge, and safety profile are consistent with the results from the studies with IV cetirizine in acute urticaria,” the authors stated.

Reference

1. Holmes JP, Dasanu CA, Peguero J, et al. Aphase 2 exploratory study of intravenous cetirizine versus intravenous diphenhydramine in the prevention of hypersensitivity infusion reactions in patients with breast cancer and other malignancies. Presented at: 38th Annual Miami Breast Cancer Conference; March 4-7, 2021; Virtual.