TY - JOUR
T1 - Avelumab first-line maintenance therapy for advanced urothelial carcinoma
T2 - comprehensive clinical subgroup analyses from the JAVELIN Bladder 100 Phase 3 trial
AU - Grivas, Petros
AU - Park, Se Hoon
AU - Voog, Eric
AU - Caserta, Claudia
AU - Gurney, Howard
AU - Bellmunt, Joaquim
AU - Kalofonos, Haralabos
AU - Ullén, Anders
AU - Loriot, Yohann
AU - Sridhar, Srikala S.
AU - Yamamoto, Yoshiaki
AU - Petrylak, Daniel P.
AU - Sternberg, Cora N.
AU - Gupta, Shilpa
AU - Huang, Bo
AU - Costa, Nuno
AU - Laliberte, Robert J.
AU - di Pietro, Alessandra
AU - Valderrama, Begoña P.
AU - Powles, Thomas
N1 - Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2023/7
Y1 - 2023/7
N2 - Background: In the phase 3 JAVELIN Bladder 100 trial, avelumab first-line (1L) maintenance + 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 following 1L platinum-based chemotherapy, leading to regulatory approval in various countries. Objective: To analyze clinically relevant subgroups from JAVELIN Bladder 100. Design, setting, and participants: Patients with unresectable locally advanced or metastatic UC without progression on 1L gemcitabine + cisplatin or carboplatin were randomized to receive avelumab + BSC (n = 350) or BSC alone (n = 350). Median follow-up was >19 mo in both arms (data cutoff October 21, 2019). This trial is registered on ClinicalTrials.gov as NCT02603432. Outcome measurements and statistical analysis: OS (primary endpoint) and PFS were analyzed in protocol-specified and post hoc subgroups using the Kaplan-Meier method and Cox proportional hazards models. Results and limitations: Hazard ratios (HRs) for OS with avelumab + BSC versus BSC alone were <1.0 across all subgroups examined, including patients treated with 1L cisplatin + gemcitabine (HR 0.69, 95% confidence interval [CI] 0.50–0.93) or carboplatin + gemcitabine (HR 0.64, 95% CI 0.46–0.90), patients with PD-L1+ tumors treated with carboplatin + gemcitabine (HR 0.67, 95% CI 0.39–1.14), and patients whose best response to chemotherapy was a complete response (HR 0.80, 95% CI 0.46–1.37), partial response (HR 0.62, 95% CI 0.46–0.84), or stable disease (HR 0.70, 95% CI 0.46–1.06). Observations were similar for PFS. Limitations include the smaller size and post hoc evaluation without multiplicity adjustment for some subgroups. Conclusions: Analyses of OS and PFS in clinically relevant subgroups were consistent with results for the overall population, further supporting avelumab 1L maintenance as standard-of-care treatment for patients with aUC who are progression-free following 1L platinum-based chemotherapy. Patient summary: In the JAVELIN Bladder 100 study, maintenance treatment with avelumab helped many different groups of people with advanced cancer of the urinary tract to live longer.
AB - Background: In the phase 3 JAVELIN Bladder 100 trial, avelumab first-line (1L) maintenance + 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 following 1L platinum-based chemotherapy, leading to regulatory approval in various countries. Objective: To analyze clinically relevant subgroups from JAVELIN Bladder 100. Design, setting, and participants: Patients with unresectable locally advanced or metastatic UC without progression on 1L gemcitabine + cisplatin or carboplatin were randomized to receive avelumab + BSC (n = 350) or BSC alone (n = 350). Median follow-up was >19 mo in both arms (data cutoff October 21, 2019). This trial is registered on ClinicalTrials.gov as NCT02603432. Outcome measurements and statistical analysis: OS (primary endpoint) and PFS were analyzed in protocol-specified and post hoc subgroups using the Kaplan-Meier method and Cox proportional hazards models. Results and limitations: Hazard ratios (HRs) for OS with avelumab + BSC versus BSC alone were <1.0 across all subgroups examined, including patients treated with 1L cisplatin + gemcitabine (HR 0.69, 95% confidence interval [CI] 0.50–0.93) or carboplatin + gemcitabine (HR 0.64, 95% CI 0.46–0.90), patients with PD-L1+ tumors treated with carboplatin + gemcitabine (HR 0.67, 95% CI 0.39–1.14), and patients whose best response to chemotherapy was a complete response (HR 0.80, 95% CI 0.46–1.37), partial response (HR 0.62, 95% CI 0.46–0.84), or stable disease (HR 0.70, 95% CI 0.46–1.06). Observations were similar for PFS. Limitations include the smaller size and post hoc evaluation without multiplicity adjustment for some subgroups. Conclusions: Analyses of OS and PFS in clinically relevant subgroups were consistent with results for the overall population, further supporting avelumab 1L maintenance as standard-of-care treatment for patients with aUC who are progression-free following 1L platinum-based chemotherapy. Patient summary: In the JAVELIN Bladder 100 study, maintenance treatment with avelumab helped many different groups of people with advanced cancer of the urinary tract to live longer.
KW - Bladder cancer
KW - Clinical trial
KW - Immunotherapy
KW - Maintenance
KW - Phase 3
KW - Randomized
KW - Urothelial carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85153942855&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2023.03.030
DO - 10.1016/j.eururo.2023.03.030
M3 - Article
C2 - 37121850
AN - SCOPUS:85153942855
SN - 0302-2838
VL - 84
SP - 95
EP - 108
JO - European Urology
JF - European Urology
IS - 1
ER -