ASCO GU 2021: Avelumab First-Line Maintenance Plus Best Supportive Care vs Best Supportive Care Alone For Advanced Urothelial Carcinoma: JAVELIN Bladder 100 Subgroup Analysis Based On Duration And Cycles Of First-Line Chemotherapy

( Avelumab first-line maintenance therapy is approved in the United States for patients with advanced urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy based on significantly prolonged overall survival versus best supportive care alone (median 21.4 months versus 14.3 months; HR 0.69, 95% CI 0.56-0.86) as reported in the phase III JAVELIN Bladder 100 trial (NCT02603432).1 However, the optimal duration of first-line chemotherapy is unknown and some patients are unable to receive six cycles. At the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), Dr. Yohann Loriot and colleagues presented results of their post hoc analysis of the JAVELIN Bladder 100 trial, specifically efficacy by duration or number of cycles of first-line chemotherapy.

Patients were eligible for JAVELIN Bladder 100 if they had unresectable locally advanced or metastatic urothelial carcinoma that had not progressed with 4-6 cycles of first-line gemcitabine plus cisplatin or carboplatin. Patients were then randomized to receive maintenance avelumab plus best supportive care or best supportive care alone within 4-10 weeks. The trial design for JAVELIN Bladder 100 is as follows:


Subgroups were defined by quartiles (Qs) for duration (<Q1 [<15.0 weeks], Q1-Q2 [15.0 to <18.0 weeks], Q2-Q3 [18.0 to <20.1 weeks], and >Q3 [>20.1 weeks]) or estimated number of cycles (4, 5, or 6) of first-line chemotherapy. Duration of chemotherapy included dosing delays/interruptions, and the decision to stop first-line chemotherapy was at the investigator’s discretion. Treatment arms were compared using an unstratified Cox proportional hazards model for overall survival. 

            The number of patients in first-line chemotherapy subgroups were generally well balanced between arms: 


Subgroups with longer exposure to prior chemotherapy appeared to have a higher proportion of patients who had received gemcitabine plus cisplatin as a first-line regimen, had achieved an objective response (complete or partial) to first-line chemotherapy, and had an ECOG performance status of 0 at randomization. Furthermore, the safety profile of avelumab was generally similar between the subgroups, irrespective of duration or cycles of first-line chemotherapy. An overall survival benefit was observed (although none were statistically significant) for avelumab plus best supportive care versus best supportive care alone across subgroups with differing durations of first-line chemotherapy:

When subgroups were stratified by number of cycles, patients receiving avelumab plus best supportive care had survival benefit across all cycles, with statistically significant improved survival if they received six cycles of chemotherapy (HR 0.66, 95% CI 0.47-0.92):


A progression-free survival benefit was also observed for avelumab best supportive care versus best supportive care alone across subgroups.

Dr. Loriot concluded this presentation of post hoc analysis of JAVELIN Bladder 100 with the following summary statements:

  • Improved overall survival was observed with avelumab first-line maintenance versus best supportive care alone irrespective of duration or cycles of first-line chemotherapy received prior to entering the trial
  • Among patients who stopped first-line chemotherapy prior to 6 cycles, avelumab first-line maintenance still provided an overall survival benefit 

Presented by: Yohann Loriot, MD, PhD, Physician Scientist, Director of Bladder Cancer Program, Gustave Roussy; Université Paris-Saclay Villejuif, France Yohann Loriot, Gustave Roussy, Université Paris-Saclay, Villejuif, France

Co-Authors: Thomas Powles, Miguel Ángel Climent Durán, Srikala S. Sridhar, Joaquim Bellmunt, Daniel Peter Petrylak, Jing Wang, Nuno Matos Costa, Robert J Laliberte, Alessandra Di Pietro, Petros Grivas, Cora N. Sternberg; Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St Bartholomew's Hospital, London, United Kingdom; Instituto Valenciano de Oncología, Valencia, Spain; Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; Department of Medical Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Yale Cancer Center, New Haven, CT; Pfizer Inc., Cambridge, MA; Pfizer, Porto Salvo, Portugal; Pfizer, Cambridge, MA; Pfizer SRL, Milan, Italy; Department of Medicine, Division of Oncology, University of Washington, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; Weill Cornell Medicine, Hematology/Oncology, New York Presbyterian Hospital, New York, NY

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Twitter: @zklaassen_md during the 2021 American Society of Clinical Oncology Genitourinary Cancers Symposium (#GU21), February 11th-February 13th, 2021

1. Powles T, Park SH, Voog E, et al. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med2020 Sept 24;383(13):1218-1230.

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JAVELIN Bladder 100: Avelumab for Previously Untreated Locally Advanced or Metastatic Urothelial Carcinoma - Thomas Powles
ASCO 2020: JAVELIN Bladder 100 Phase III Results: Maintenance Avelumab + Best Supportive Care vs BSC Alone After Platinum-Based First-Line Chemotherapy in Advanced Urothelial Carcinoma