Additive Antihistamines May Improve Metastatic Bladder Cancer Outcomes

Antihistamines are associated with improvements in progression-free events and survival outcomes for patients with metastatic urothelial carcinoma (mUC) receiving Tecentriq (atezolizumab), research has shown.

Drawing on data from 896 patients from the phase 2 IMvigor210 trial and phase 3 IMvigor211 trial, researchers published their findings in Urologic Oncology: Seminars and Original Investigations. They found that at two years, the overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) probabilities were 46%, 48% and 23%, respectively, among patients who received antihistamines, and 23%, 32% and 13% for those who did not.

After excluding patients who experienced immune-oncology-related side effects, researchers found a 22% reduction in the risk of cancer-specific death and a 29% reduction in the risk of death from any cause.

The median follow-up time for patients receiving antihistamines was 17.7 months and 7.7 months for patients who did not receive them.

“In this study we investigated the impact of antihistamines on oncological outcomes among patients with [metastatic urothelial carcinoma] treated with second-line [Tecentriq] in two randomized clinical trials. We found that patients [who] received antihistamines concomitant to [immune-oncology] had longer OS, CSS and PFS relative to individuals who did not receive antihistamine medications,” wrote Dr. Giuseppe Fallara and colleagues in the study.

Fallara is a urologist in the Department of Urology at the IRCCS European Institute of Oncology in Milan, Italy.

Among patients who received antihistamines, the median OS was 17.7 months versus 8.1 months for those who did not. Likewise, the median PFS times were 4.9 and 2.3 months, respectively, and the CSS times were 22.8 and 9.3 months, respectively.

Patients with locally advanced UC or mUC generally face poor prognoses, with a five-year OS rate of approximately 6%, the researchers stated.

However, they noted that previous data suggest that antihistamines may improve cancer outcomes, particularly when administered in conjunction with immunotherapy, by reversing T cell dysfunction.

Tecentriq, a type of immunotherapy known as an immune checkpoint inhibitor, binds to the protein PD-L1 on the surface of some cancer cells, which prevents cancer cells from suppressing the immune system, according to the National Cancer Institute.

Of the 896 patients whose data were utilized in the study, 155, or 17%, used antihistamines during the two trials in question. Researchers reported that overall, 645 patients died of cancer-related causes and 59 died of other causes. Seven hundred patients experienced disease progression while on treatment.

Fallara and his colleagues acknowledged that their study had several limitations, including that researchers did not have detailed data regarding the timing, duration, type of antihistamine and reasons for antihistamine use.

“In conclusion, using individual patient data from the IMvigor210 and 211 trials, we found that concomitant use of antihistamines was associated with prolonged progression-free, cancer-specific and overall survival in patients treated with [Tecentriq],” Fallara and colleagues wrote. “Our results showed a positive association between antihistamine use and oncologic outcomes in patients with mUC treated with [immunotherapy]. This effect deserves further prospective investigation, ideally with a randomized controlled trial of antihistamine versus no antihistamine use.”

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