Avelumab First-Line Maintenance for Advanced Urothelial Carcinoma: Results From the JAVELIN Bladder 100 Trial After ≥2 Years of Follow-Up

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Initial results from the phase III JAVELIN Bladder 100 trial (ClinicalTrials.gov identifier: NCT02603432) showed that avelumab first-line (1L) maintenance plus best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) versus BSC alone in patients with advanced urothelial carcinoma (aUC) who were progression-free after 1L platinum-containing chemotherapy. Avelumab 1L maintenance treatment is now a standard of care for aUC. Here, we report updated data with ≥ 2 years of follow-up in all patients, including OS (primary end point), PFS, safety, and additional novel analyses. Patients were randomly assigned 1:1 to receive avelumab plus BSC (n = 350) or BSC alone (n = 350). At data cutoff (June 4, 2021), median follow-up was 38.0 months and 39.6 months, respectively; 67 patients (19.5%) had received ≥2 years of avelumab treatment. OS remained longer with avelumab plus BSC versus BSC alone in all patients (hazard ratio, 0.76 [95% CI, 0.63 to 0.91]; 2-sided P = .0036). Investigator-assessed PFS analyses also favored avelumab. Longer-term safety was consistent with previous analyses; no new safety signals were identified with longer treatment duration. In conclusion, longer-term follow-up continues to show clinically meaningful efficacy benefits with avelumab 1L maintenance plus BSC versus BSC alone in patients with aUC. An interactive visualization of data reported in this article is available.

FIG 1.

Efficacy analyses showing (A) Kaplan-Meier estimate of OS in the overall population, (B) forest plot of OS subgroup analysis, and (C) Kaplan-Meier estimate of investigator-assessed PFS in the overall population. (B) Unless otherwise stated, all analyses are unstratified, and analyses in subgroups with unreported or unknown creatinine clearance or 1L chemotherapy regimen are not shown because of the small number of patients in these subgroups. ^aHRs and CIs were calculated using a Cox proportional hazards model. ^bStratified by best response to 1L chemotherapy (CR or PR v SD) and metastatic disease site when initiating 1L chemotherapy (visceral v nonvisceral). ^cPatients who switched platinum regimens while receiving 1L chemotherapy. 1L, first-line; BSC, best supportive care; CR, complete response; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; OS, overall survival; PFS, progression-free survival; PR, partial response; SD, stable disease.