56 A Phase 2 Exploratory Study of Intravenous Cetirizine Versus Intravenous Diphenhydramine in the Prevention of Hypersensitivity Infusion Reactions in Patients With Breast Cancer and Other Malignancies
Jarrod P. Holmes, MD, FACP1; Constantin A. Dasanu, MD, PhD2; Julio Peguero, MD3; Ahmed Ayad, MD3; R. Campbell Garland, DO4; Anne O’Shea, MD5; G. Travis Clifton, MD5; George Peoples, MD, FACS6; Stacia Young, PharmD, BCOP, MBA7; Teresa Yang, BSN, MBA; Janine North, BS; Nancy Joseph-Ridge, MD7
1St. Joseph Health Medical Group Sonoma, Santa Rosa, CA
2Lucy Curci Cancer Center, Eisenhower Health, Rancho Mirage, CA
3Oncology Consultants, Houston, TX
4Baylor Scott & White Medical Center – Temple, Temple, TX
5Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, TX
6Cancer Vaccine Development Program, San Antonio, TX
7TerSera Therapeutics, Carmel, CA
Background
Antihistamine pretreatment for drug-induced hypersensitivity infusion reactions (IRs) is recommended with certain breast cancer treatments, including paclitaxel.1-5 The only second-generation intravenous (IV) antihistamine currently available is IV cetirizine.6 Intravenous cetirizine was shown to treat acute urticaria comparably to IV diphenhydramine, with fewer adverse effects (AEs), and may be effective for pretreatment of IRs.7
Materials and Methods
This randomized, double-blind, phase 2 study evaluated pretreatment with single-dose IV cetirizine 10 mg versus IV diphenhydramine 50 mg in 34 patients receiving paclitaxel, rituximab (Rituxan), its biosimilar, or obinutuzumab (Gazyva) (first cycle, retreatment after 6 months or in patients with persistent IRs). The primary objective of the study was to compare the incidence of IRs after pretreatment with the 2 medications. The key secondary end point was sedation score due to IV antihistamines. The study also evaluated the need for rescue medication and the time to readiness for discharge. During and following infusion, IR symptoms, such as flushing, urticaria, and dyspnea, were assessed. Sedation was measured by health care providers on a scale of 0 to 4 (where 0 = no sedation and 4 = extreme sedation). Due to the exploratory nature of the study, no formal statistical analyses were planned.
Results
Adult patients primarily with hematologic and solid tumor malignancies, including breast cancer, were enrolled between March 26, 2020 and November 23, 2020. The median age was 65 years for the IV cetirizine group and 67 years for the IV diphenhydramine group. The number of patients who experienced an IR was 2 out of 17 (11.8%) with IV cetirizine versus 4 out of 17 (23.5%) with IV diphenhydramine. Mean sedation scores (standard deviation [SD]) in the IV cetirizine group were 0.47 (0.80), 0.63 (0.89), and 0.18 (0.39), compared with 1.00 (1.46), 0.76 (1.13), and 0.35 (1.00) in the IV diphenhydramine group at 1 hour, 2 hours, and discharge, respectively. Results were similar with patient-rated sedation scores. Mean time for readiness for discharge was 25 minutes shorter with IV cetirizine versus IV diphenhydramine. There were fewer treatment-related AEs with IV cetirizine (1 event) than with IV diphenhydramine (3 events).
Conclusion
This was the first prospective, randomized, controlled trial evaluating IV antihistamine pretreatment for the prevention of IRs. The results of this study demonstrated that IV cetirizine was as effective as IV diphenhydramine for the prevention of IRs due to paclitaxel or an anti-CD20 agent, with less sedation and fewer treatment-related AEs.
References:
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2. Joerger M. Prevention and handling of acute allergic and infusion reactions in oncology. Ann Oncol. 2012;23(suppl 10):x313–x319. doi:10.1093/annonc/mds314
3. Paclitaxel. Package insert. Hospira Inc; 2018.
4. NCCN. Clinical Practice Guidelines in Oncology. Ovarian cancer including fallopian tube cancer and primary peritoneal cancer, version 1.2021. Accessed March 18, 2021. https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf
5. Roselló S, Blasco I, García Fabregat L, Cervantes A, Jordan K; ESMO Guidelines Committee. Management of infusion reactions to systemic anticancer therapy: ESMO Clinical Practice Guidelines. Ann Oncol. 2017;28(suppl_4):iv100-iv118. doi:10.1093/annonc/mdx216
6. QUZYTTIR. Package insert. TerSera Therapeutics LLC; 2019.
7. Abella BS, Berger WE, Blaiss MS, et al. Intravenous cetirizine versus intravenous diphenhydramine for the treatment of acute urticaria: a phase III randomized controlled noninferiority trial. Ann Emerg Med. 2020;76(4):489-500. doi:10.1016/j.annemergmed.2020.05.025
