Antihistamines Added to IO Associated with Longer Survival in Urothelial Carcinoma

Retrospective analyses found that antihistamines added to atezolizumab yielded a 46% OS rate, a 48% CSS rate, and a 23% PFS rate in patients with metastatic urothelial carcinoma.

Concomitant antihistamines when administered to patients receiving atezolizumab (Tecentriq) resulted in enhanced overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS) in the second-line treatment of patients with metastatic urothelial carcinoma, according to a retrospective analysis published in Urologic Oncology.¹

At the 2-year mark, patients who received antihistamines demonstrated a probability of OS in 46% vs 23% in those who did not receive antihistamines; of CSS in 48% vs 32%, respectively; and of PFS in 23% vs 13%.

The median OS for those who received antihistamines was 17.7 months (IQR, 12.7-24.5) vs 8.1 months (IQR, 7.1-8.9) in those who didn’t (P <.001); the median PFS was 4.9 months (IQR, 4.1-6.7) vs 2.3 months (IQR, 2.2-2.7), respectively (P <.001); and the median CSS was 22.8 months (IQR, 16.4-26.4) vs 9.3 months (IQR, 7.6-10.1), respectively (P <.001).

With the multivariable Cox analysis, prolonged OS (HR, 0.59; 95% CI, 0.47-0.74; P <.001) and prolonged PFS (HR, 0.70; 95% CI, 0.57-0.87; P = .001) were associated with antihistamine use compared with those who did not use antihistamines; CSS was also longer for those who used antihistamines (sHR, 0.58; 95% CI, 0.45-0.75; P <.001). Sensitivity analyses with patients who experienced adverse events (AEs) and received antihistamines excluded also demonstrated prolonged CSS (sHR, 0.78; 95% CI, 0.59-0.98; P = .031) and prolonged OS (HR, 0.71; 95% CI, 0.52-0.94; P = .021).

“Our results showed a positive association between antihistamines use and oncologic outcomes in patients with [metastatic urothelial carcinoma] treated with [immunotherapy],” lead study author Alberto Martini, MD, assistant professor of Clinical Urology at The University of Cincinnati, wrote in the study.¹ “This effect deserves further prospective investigation ideally with a randomized controlled trial of antihistamine vs no antihistamine use.”

Trial data comes from the intention-to-treat population of the phase 2 IMvigor210 trial (NCT02108652) evaluating second-line atezolizumab with antihistamines in metastatic urothelial carcinoma and the atezolizumab arm of the phase 3 IMvigor211 trial (NCT02302807) evaluating second-line atezolizumab compared with chemotherapy in metastatic urothelial carcinoma.^2,3

Overall, 155 patients received antihistamines vs 741 patients who did not. The median age in each group was 68 years (IQR, 62-75) and 67 years (IQR, 60-73), respectively; 41% and 40% were female; the median body mass index was 27.4 (IQR, 23.6-31.5) and 26.0 (IQR, 23.3-29.8). Also, 46% and 41% of patients received at least 2 prior lines of systemic therapy and 40% and 48% received 1 prior line of systemic therapy; systemic therapy was cisplatin only for 54.0% and 57.0%, carboplatin only for 23.0% and 24.0%, cisplatin plus carboplatin for 7.7% and 6.9%, and other combinations for 1.3% and 1.3%.

The majority of patients had histology of transitional cell carcinoma (90% in antihistamine patients and 90% in non-antihistamine patients), tumor stage T1/a/is/x (32% vs 36%), 2 metastasis sites (39% vs 33%), visceral metastasis (77% vs 77%), and no liver metastasis (76% vs 73%).

The median follow-up was 17.7 months (IQR, 6.7-32.4) for those who received antihistamines and 7.7 months (IQR, 2.8-18.2) for those who didn’t.

Via the sensitivity analysis that excluded those who developed an immunotherapy-related AE, antihistamines led to prolonged CSS with a median of 18.2 months (IQR, 13.4-21.1) and 9.3 (IQR, 7.6-10.1), respectively, and prolonged OS with medians of 18.1 (IQR, 12.7-24.8) and 8.5 months (IQR, 7.3-9.1). PFS was not significantly changed with medians of 4.7 months (IQR, 2.3-7.0) and 2.4 months (IQR, 1.9-3.1).

The cumulative incidence curves for CSS and the Kaplan-Meier curves for PFS and OS demonstrated median a CSS of 21.3 months (IQR, 15.1-26.2) with antihistamines and 8.9 months (IQR, 7.2-9.5) without and a median OS of 18.9 months (IQR, 13.4-26.8) and 8.5 months (IQR, 7.9-9.6).

Supplementary analysis from the control arm of IMvigor211 did not find a correlation between OS, CSS, or PFS and antihistamine use in the multivariable survival analysis. Analyses excluding cohort 1 in IMvigor210 found that OS, CSS, and PFS were higher with antihistamine use in patients who progressed after platinum-based chemotherapy.

References

1. Martini A, Fallara G, Belladelli F, et al. Concomitant antihistamine administration is associated with improved survival outcomes in patients with locally advanced or metastatic urothelial carcinoma treated with atezolizumab. Analysis of individual participant data from IMvigor210 and IMvigor211. Urol Onc. Available online January 9, 2025. doi:10.1016/j.urolonc.2024.12.267
2. A study of atezolizumab in participants with locally advanced or metastatic urothelial bladder cancer (Cohort 2). ClinicalTrials.gov. Updated March 28, 2024. Accessed February 24, 2025. https://tinyurl.com/4byc74vh
3. A study of atezolizumab compared with chemotherapy in participants with locally advanced or metastatic urothelial bladder cancer [IMvigor211]. ClinicalTrials.gov. Updated August 1, 2019. Accessed February 24, 2025. https://tinyurl.com/3wmz3ujm