As reported in the journal Urologic Oncology: Seminars and Original Investigations by Fallara et al, an analysis of individual patient data from the IMvigor210 and IMvigor211 trials revealed that concomitant second-line treatment of locally advanced or metastatic urothelial carcinoma with antihistamines and atezolizumab improved oncologic and survival outcomes.
The investigators commented: “In the second-line setting, in light of the results of [the] KEYNOTE-045, CheckMate-275, and IMvigor211 trials, pembrolizumab, nivolumab, and atezolizumab, respectively, were approved by the European Medicines Agency and the U.S. Food and Drug Administration; however, the response rate to these therapies is still suboptimal. Preclinical and clinical data suggest that antihistamines may improve cancer outcomes in different settings, particularly when immune-oncology [compounds are] administered, by reversing T-cell dysfunction. [Prior to this study], the effect of antihistamines in second-line immune-oncology treatment for metastatic urothelial carcinoma had not been investigated.”
Study Details
Both the phase II IMvigor210 and phase III IMvigor211 trials enrolled patients with locally advanced or metastatic urothelial carcinoma who experienced disease progression after undergoing platinum-based chemotherapy. The IMvigor210 trial assessed atezolizumab in a single-arm design, whereas the randomized IMvigor211 trial compared the agent with chemotherapy.
The investigators analyzed data from the intention-to-treat population of IMvigor210 and the atezolizumab arm of IMvigor211. Among 896 identified patients, 155 (17%) received antihistamines while also receiving atezolizumab.
Using multivariable Cox or competing-risks regression models, the investigators predicted progression-free, overall, and cancer-specific survival. The impact of antihistamines on outcomes was evaluated after adjusting for potential confounders.
Key Findings
Patients who did vs did not receive antihistamines were found to have longer overall survival (hazard ratio [HR] = 0.59, 95% confidence interval [CI] = 0.47–0.74; P < .001), progression-free survival (HR = 0.70, 95% CI = 0.57–0.87; P = .001), and cancer-specific survival (stratified HR = 0.58, 95% CI = 0.45–0.75; P < .001). A sensitivity analysis, which excluded those who experienced adverse events with antihistamines, demonstrated similar findings of prolonged durations of cancer-specific survival (stratified HR = 0.78, 95% CI = 0.59–0.98; P = .031) and overall survival (HR = 0.71, 95% CI = 0.52–0.94; P = .021).
“Concomitant antihistamines administration was associated with improved overall survival, cancer-specific survival, and progression-free survival in patients receiving atezolizumab as second-line treatment,” the investigators concluded. “This effect deserves further prospective investigation ideally with a randomized controlled trial of antihistamine vs no antihistamine use.”
Alberto Martini, MD, of The University of Texas MD Anderson Cancer Center, Houston, is the corresponding author of the Urologic Oncology: Seminars and Original Investigations article.
Disclosure: The study was funded in part by a grant from the National Cancer Institute. For full disclosures of the study authors, visit sciencedirect.com.
