AUA 2021: Avelumab First-Line Maintenance Plus Best Supportive Care vs Best Supportive Care Alone for Advanced Urothelial Carcinoma: Analysis of Time to End of Next-Line Therapy in JAVELIN Bladder 100

( As a follow-up to the JAVELIN BLADDER 100 trial,1 which demonstrated the efficacy of avelumab as a first line maintenance therapy for patients with advanced urothelial carcinoma who have NOT progressed on first line platinum based chemotherapy, Dr. Bellmunt and colleagues herein report a secondary analysis of time to end of next-line therapy in patients treated with avelumab vs. best supportive care (BSC).

As a reminder, the JAVELIN Bladder 100 was a landmark trial,1 which demonstrated an overall survival (OS) benefit to the use of avelumab as a first-line (1L) maintenance for patients (pts) with advanced urothelial carcinoma (UC) that had not progressed with 1L platinum-based chemotherapy. This was fully reported on Urotoday. Overall survival at 1 year was 71.3% in the avelumab group and 58.4% in the control group (median overall survival, 21.4 months vs. 14.3 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.86; P = 0.001). 

In the original study, OS was prolonged despite the more frequent use of subsequent anticancer therapy in the BSC alone arm (42.3% in the avelumab+BSC arm vs 61.7% in the BSC alone arm), most commonly with immune checkpoint inhibitors (6.3% vs 43.7%, respectively). A summary of the next-line therapies utilized is seen below:



As such, in this analysis, the authors aimed to analyze the time to end of next-line therapy (for any reason) in the randomized trial population to determine the impact of avelumab on subsequent therapy. 

In JAVELIN Bladder 100 (NCT02603432), eligible pts had unresectable locally advanced or metastatic UC without progression with 4-6 cycles of 1L gemcitabine and either cisplatin or carboplatin. The primary endpoint was OS from randomization, assessed in 2 populations: all pts and pts with PD-L1+ tumors (Ventana SP263). In this exploratory analysis, time from randomization until end of next-line treatment received after progression (due to death or discontinuation) was assessed.

A total of 700 pts were randomized 1:1 to avelumab 1L maintenance+BSC or BSC alone. Jumping straight to this conclusion, among all randomized pts, time to end of next-line therapy was prolonged in the avelumab+BSC arm vs the BSC alone arm (Table).




The KM curve is seen below for all patients:



When looking at the patients from a PD-L1 stratification, time to end of next-line therapy was also longer in the avelumab+BSC arm vs the BSC alone arm in pts with PD-L1+ tumors (n=358) or PD-L1− tumors (n=270). The KM curve as seen below:




When looking at subgroups, all subgroups appeared to maintain this benefit:



Based on this, Dr. Bellmunt and colleagues conclude that patients who received avelumab 1L maintenance+BSC had prolonged time to end of next-line treatment vs those who received BSC alone, irrespective of PD-L1 status, which provides further evidence of the efficacy of a maintenance approach with avelumab in pts with advanced UC that have not progressed with 1L platinum-based chemotherapy.


This is already a paradigm-shifting study, but this further validates this approach.



1. Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulović S, Demey W, Ullén A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18. PMID: 32945632.

Presented by: Joaquim Bellmunt, MD, Ph.D., Associate Professor, Medicine, Harvard Medical School, Director, Bladder Cancer Program , Beth Israel Deaconess Medical Center

Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Assistant Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @tchandra_uromd on Twitter during the 2021 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 – Mon, Sep 13, 2021.



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