Sustained overall survival benefit with avelumab maintenance in advanced urothelial carcinoma

September 2023 Cancer trials Andrea Enguita
African American doctor showing patient digital tablet

In the phase III JAVELIN Bladder 100 trial, avelumab first-line (1L) maintenance with best supportive care (BSC) significantly improved overall survival and progression-free survival in advanced urothelial carcinoma patients who were progression-free after 1L platinum-containing chemotherapy. Recently published in the Journal of Clinical Oncology, the updated results with more than 2 years of follow-up continue to support the use of avelumab 1L maintenance plus BSC over BSC alone in these patients.

Bladder cancer is one of the most common cancers worldwide, with more than 500,000 new cases and around 200,000 deaths yearly.1 Urothelial carcinoma (UC), the most common type, primarily originates in the bladder and is marked by genomic instability, elevated PD-L1 expression, DNA damage-response mutations, and a high tumour mutational burden. These characteristics render UC highly responsive to immune checkpoint inhibitors (ICI). Initial results from the phase III JAVELIN Bladder 100 trial showed that avelumab first-line (1L) maintenance plus best supportive care (BSC) significantly prolonged overall survival (OS) and progression-free survival (PFS) compared to BSC alone in patients with advanced UC (aUC) who were progression-free after 1L platinum-containing chemotherapy.2 This report provides updated data, including OS, PFS and safety, with more than 2 years of follow-up in all patients.3


The phase 3 JAVELIN Bladder 100 trial enrolled patients with locally advanced or metastatic UC who were progression-free after 4-6 cycles of 1L chemotherapy. After a 4-10-week interval from the last chemotherapy dose, patients were randomly assigned (1:1) to receive avelumab plus BSC (avelumab arm) or BSC alone (control arm), stratified by visceral/nonvisceral metastatic disease site at chemotherapy initiation and response/stable disease with chemotherapy (n=350 each). Treatment continued until patient withdrawal, confirmed progression, unacceptable toxicity, or other criteria for discontinuation occurred.2,3 The primary endpoint was OS. Secondary endpoints included PFS, objective response, time to response, duration of response, disease control, and safety.

Study findings

At data cutoff, the median follow-up in the avelumab and control arms was 38.0 and 39.6 months, respectively (≥2 years in all patients). In the overall population, OS was prolonged with avelumab as compared to BSC alone (median OS 23.8 vs. 15.0 months, respectively; HR[95%CI]: 0.76[0.63-0.91]; p= 0.0036). The 2-year OS rates were 49.8% vs. 38.4%. OS analyses favoured avelumab across all subgroups, including those defined by chemotherapy regimen and best response to chemotherapy. The median PFS was also extended in those patients receiving avelumab (5.5 vs. 2.1 months, respectively; HR[95%CI]: 0.54[0.46-0.64]; p <0.0001), with 2-year PFS rates of 23.4% vs. 7.1%, respectively. Among responders, the median duration of response was 28.4 months in the avelumab arm and 26.9 months in the control arm. Subsequent anticancer drug therapy (second-line or later) was received by 52.9% vs. 72.0% of patients in the avelumab and control arms, respectively, including a PD-1/PD-L1 inhibitor in 11.4% and 53.1%, respectively. Longer-term safety was consistent with previous analyses and no new safety signals were identified with longer treatment duration.

In conclusion, longer-term results from JAVELIN Bladder 100 further support the recommendation of avelumab 1L maintenance as the standard of care for patients with aUC that has not progressed with 1L platinum-containing chemotherapy.


  1. Wood LS, Conway D, Lapuente M, et al. Avelumab First-Line Maintenance Treatment in Advanced Bladder Cancer: Practical Implementation Steps for Infusion Nurses. J Infus Nurs. 2022 May; 45(3): 142–53.
  2. Powles T, Hoon Se, Voog E, et al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020;383(13):1218-30.
  3. Powles T, Park SH, Caserta C, et al. Avelumab First-Line Maintenance for Advanced Urothelial Carcinoma: Results From the JAVELIN Bladder 100 Trial After ≥2 Years of Follow-Up. J Clin Oncol. 2023;41(19):3486-92.