Gradishar Highlights Cetirizine as Management Tool for Hypersensitivity Infusion Reactions in Breast Cancer and Beyond

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Partner | Cancer Centers | <b>Robert H. Lurie Comprehensive Cancer Center of Northwestern University Northwestern Medicine</b>

William Gradishar, MD, discusses the phase 2 data evaluating the activity with IV cetirizine and its potential use in patients with breast cancer.

Intravenous (IV) cetirizine (Quzyttir) demonstrated equivalent effectiveness compared with IV diphenhydramine at preventing hypersensitivity infusion reactions (IRs) in patients with breast cancer as well as those with other malignancies, explained William Gradishar, MD.

Results from a phase 2 trial (NCT04189588) also showed that IV cetirizine was associated with less sedation, less time in clinic after treatment, and fewer treatment-related AEs than IV diphenhydramine. The rate of IRs in patients who received IV cetirizine was 11.8% vs 17.6% those who received IV diphenhydramine. Additionally, the mean sedation scores at 1 hour, 2 hours, and at discharge in those receiving IV cetirizine was 0.5 (0.72), 0.6 (0.61), and 0.1 (0.33), compared with 1.3 (1.26), 0.9 (1.14), and 0.4 (0.71) for those on IV diphenhydramine, respectively.

In terms of time spent in clinic, the median time for readiness for discharge was 24 minutes quicker with IV cetirizine at 4 hours and 18 minutes, compared with 4 hours and 42 minutes with IV diphenhydramine.

Additionally, fewer treatment-emergent adverse effects (TEAEs) were observed in the IV cetirizine (n = 8) vs IV diphenhydramine arm (n = 9), and the most common TEAEs in the IV cetirizine cohort included insomnia, dyspepsia, and malaise. The most common TEAEs in the IV diphenhydramine cohort were diarrhea, injection site pain, headache, somnolence, dizziness, and lightheadedness.

“The purpose was to look at several different end points to see if there was a difference in terms of not only hypersensitivity reactions, but adverse effects [AEs] that we relate to the drugs themselves, such as drowsiness or time that the patient spends in the clinic,” Gradishar noted.

In an interview with OncLive, Gradishar, chief of hematology and oncology, Department of Medicine, Betsy Bramsen Professorship of Breast Oncology, and a professor of medicine (hematology and oncology) at Northwestern University Feinberg School of Medicine, discussed the phase 2 data evaluating the activity with IV cetirizine and its potential use in patients with breast cancer.

OncLive: What is the importance of antihistamine pretreatment for drug-induced hypersensitivity and fusion reactions?

Gradishar: In any patient getting chemotherapy or, more broadly, therapy for cancer, we try to minimize the AEs. Some AEs that can be very distressing to patients, depending on how severe they are, are hypersensitivity reactions. As a breast cancer physician, we see these on occasion, particularly with taxane therapy, and oncologists who take care of hematologic malignancies encounter them when they are using anti-CD20 therapies, such as rituximab [Rituxan].

These are not typically high-grade phenomena, [though] occasionally they can be. The most disastrous are anaphylactic reactions, but more commonly they present as symptoms where patients feel flushed, or have some tightness in the chest or shortness of breath as it progresses. Anything we can do to even keep low-grade hypersensitivity reactions is something that we seek to do. As a breast cancer doctor, we typically premedicate all patients who are getting typical taxanes—like paclitaxel or docetaxel—in an effort to reduce those AEs.

What was the rationale for this phase 2 study that examined IV cetirizine and IV diphenhydramine to prevent hypersensitivity IRs?

The rationale of this study was to determine [whether the investigators] could substitute a different medication for the typical agent we use—diphenhydramine—to reduce the risk of hypersensitivity reactions, may prove to be equally effective, with potentially fewer AEs.

This was a very small study that looked to recruit patients with both hematologic malignancies as well as solid tumors, including breast cancer, and randomize them to either IV cetirizine or IV diphenhydramine.

What methods were utilized in this trial?

Typically, when we are treating patients with chemotherapy, such as taxanes—or if the patient has a hematologic malignancy, anti-CD20 drugs such as rituximab—they will typically receive premedication prior to receiving a cancer therapeutic. In this case, patients were randomized either to IV cetirizine or IV diphenhydramine.

The end points were to determine whether or not hypersensitivity was in any way different between the 2 groups. Some of the other secondary endpoints [included] sedation and the time from injecting the agent until the patient exited the clinic. In other words, did patients have to spend more or less time, depending on what premedication they received?

What were the key findings?

Data found that the use of IV cetirizine vs IV diphenhydramine was equally effective in terms of reducing the risk of hypersensitivity IRs. There were more patients with hematologic malignancies [enrolled] on this small trial than with solid tumors—for example, there were only a handful of patients with breast cancer—but the risk of developing any level of hypersensitivity reaction was essentially equivalent between the 2 groups.

It was noted that the secondary end points also supported the idea that IV cetirizine could be used with sedation scores at several different time points, and this was favored in the IV cetirizine arm compared with IV diphenhydramine.

Finally, the amount of time that patients have to spend in the clinic with 1 drug vs the other [was examined]. Presumably, if a patient is drowsy or had some other AE, would that delay their departure from the clinic? In other words, are you freeing up some of the patient's time by using 1 premedication over the other? There was a suggestion that IV cetirizine allowed a patient to exit the clinic in a quicker amount of time, [therefore demonstrating] a shorter period of total time in the clinic.

What factors might help to determine if 1 of these premedications is better for an individual patient over another?

A bigger study would help define more definitively whether 1 drug is better than the other. The end points that we are looking at are sometimes a little bit softer. In other words, when you are trying to assess sedation, the physician is making a judgement and the patient is making a judgment, so it is not as though you are looking at a laboratory study where it is very quantitative. It is more of a qualitative endpoint.

Harder end points are whether there was a difference in the number of patients who experienced hypersensitivity reactions, and that was relatively equivalent in this trial, so you would need a much bigger trial to really define whether there truly is a difference.

Finally, the time that a patient spends in clinic [is dependent on many factors, including whether it is] busier at 1 time of the day than the other. You would have to have everything very well controlled to be confident that you were showing a distinction between the 2 drugs, in terms of one allowing the patient to leave quicker than the other. It would require a much more rigorous evaluation to determine that.

What you can say at the end of the day is, based on this study, IV cetirizine looks similar in terms of the primary endpoint of reducing the risk of hypersensitivity reactions compared with IV diphenhydramine. With respect to the secondary end points, you need more data to make any convincing judgment.


  1. Holmes JP, Dasanu CA, Peguero J, et al. 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. Presented at: 38th Annual Miami Breast Cancer Conference; March 4-7, 2021; virtual.