PRIMARY, LONG-TERM, & LONG-TERM EXPLORATORY OS ANALYSES

JAVELIN Bladder 100 Trial—a Phase 3, randomized, open-label, multicenter study in patients with unresectable, locally advanced or metastatic urothelial carcinoma that did not progress with first-line platinum-containing chemotherapy (N=700)1,2

 

BAVENCIO + best supportive care (BSC) demonstrated superior overall survival (OS) vs BSC alone1,2

OS in all randomized patients, data cutoff October 21, 20191

4-6 cycles platinum-containing chemotherapy1; 4-10 weeks treatment-free interval2

OS was measured post-randomization (after chemotherapy and treatment-free interval)1
 

Graph Showing BAVENCIO® (avelumab) + BSC and BSC Alone, with 31% Reduction in Risk of Death vs. BSC Alone
Graph Showing BAVENCIO® (avelumab) + BSC and BSC Alone, with 31% Reduction in Risk of Death vs. BSC Alone

Median duration of follow-up was 19.6 months (95% CI: 18.0, 20.6) in the BAVENCIO + BSC arm and 19.2 months (95% CI: 17.4, 21.6) in the BSC-alone arm3

  • A pre-planned interim analysis (IA) occurred with a data cutoff of October 21, 2019. The IA was considered as the primary analysis of the trial since the primary endpoint was met4 
  • Among all randomized patients, consistent results were observed across the prespecified subgroup of CR/PR vs SD to first-line chemotherapy2 
  • 44% of patients in the BSC arm received another PD-1/PD-L1 checkpoint inhibitor as subsequent therapy vs 6% of patients in the BAVENCIO + BSC arm2

*P-value based on stratified log-rank.

Using the VENTANA PD-L1 (SP263) assay, PD-L1-positive status was defined as PD-L1 expression in ≥25% of tumor cells or in ≥25% or 100% of tumor-associated immune cells if the percentage of immune cells was >1% or ≤1%, respectively. If none of these criteria were met, PD-L1 status was considered negative.1

CI=confidence interval; CR=complete response; NE=not estimable; PD-1=programmed death-1 receptor; PD-L1=programmed death ligand-1; PR=partial response; SD=stable disease.

Primary overall survival (OS) results—PD-L1-positive patients1†

BAVENCIO + best supportive care (BSC) demonstrated superior OS vs BSC alone in PD-L1-positive patients1
OS IN PATIENTS WITH PD-L1-POSITIVE TUMORS (N=358), DATA CUTOFF OCTOBER 21, 20191

Hazard ratio (HR): 0.56
(95% CI: 0.40, 0.79)
2-sided P-value*<0.001

Median OS: NE
(95% CI: 20.3, NE)
BAVENCIO + BSC (n=189)

VS

Median OS: 17.1 months
(95% CI: 13.5, 23.7)
BSC alone (n=169)

PD-L1-negative tumors (exploratory analysis)1

In patients with PD‑L1‑negative tumors (n=270, 39%), the OS hazard ratio was 0.85 (95% CI: 0.62, 1.18)

*P-value based on stratified log-rank.

Using the VENTANA PD-L1 (SP263) assay, PD-L1-positive status was defined as PD-L1 expression in ≥25% of tumor cells or in ≥25% or 100% of tumor-associated immune cells if the percentage of immune cells was >1% or ≤1%, respectively. If none of these criteria were met, PD-L1 status was considered negative.1

CI=confidence interval; CR=complete response; NE=not estimable; PD-1=programmed death-1 receptor; PD-L1=programmed death ligand-1; PR=partial response; SD=stable disease.

LIMITATIONS: Although the follow-up overall survival (OS) analysis was prespecified, no formal hypothesis testing was performed given that the OS endpoint was met in the initial interim analysis. Therefore, no conclusions can be drawn from the follow-up OS analysis.4

BAVENCIO + best supportive care (BSC) vs BSC alone4

Long-term OS in all randomized patients, data cutoff June 4, 20214

4-6 cycles platinum-containing chemotherapy4; 4-10 weeks treatment-free interval4

OS was measured post-randomization (after chemotherapy and treatment-free interval)4

longterm-os-analysis
longterm

Median duration of follow-up was 38.0 months (95% CI: 36.1, 40.5) in the BAVENCIO + BSC arm and 39.6 months (95% CI: 36.2, 41.7) in the BSC-alone arm4,5

53% of patients in the BSC arm received another PD-1/PD-L1 checkpoint inhibitor as subsequent therapy vs 11% of patients in the BAVENCIO + BSC arm4

*Using the VENTANA PD-L1 (SP263) assay, PD-L1-positive status was defined as PD-L1 expression in ≥25% of tumor cells or in ≥25% or 100% of tumor-associated immune cells if the percentage of immune cells was >1% or ≤1%, respectively. If none of these criteria were met, PD-L1 status was considered negative.4

BSC=best supportive care; CI=confidence interval; PD-1=programmed death-1 receptor; PD-L1=programmed death ligand-1.

  • A pre-planned interim analysis (IA) occurred with a data cutoff of October 21, 2019. The IA was considered as the primary analysis of the trial since the primary endpoint was met3
  • Among all randomized patients, consistent results were observed across the prespecified subgroup of CR/PR vs SD to first-line chemotherapy
  • 44% of patients in the BSV arm received another PD-1/PD-L1 checkpoint inhibitor as subsequent therapy vs 6% of patients in the BAVENCIO + BSC arm

Long-term overall survival (OS) results—PD-L1-positive patients

BAVENCIO + BSC vs BSC alone in PD-L1-positive patients4*
LONG-TERM OS IN PATIENTS WITH PD-L1-POSITIVE TUMORS (N=358), DATA CUTOFF JUNE 4, 20214

Hazard ratio (HR): 0.69
(95% CI: 0.52, 0.90)

Median OS: 30.9 months
(95% CI: 24.0, 39.8)
BAVENCIO + BSC (n=189)

vs

Median OS: 18.5 months
(95% CI: 14.1, 24.2)
BSC alone (n=169)

PD-L1-negative tumors (exploratory analysis)4,6*

In patients with PD-L1-negative tumors (n=270, 39%), the OS hazard ratio was 0.82 (95% CI: 0.62, 1.09)

*Using the VENTANA PD-L1 (SP263) assay, PD-L1-positive status was defined as PD-L1 expression in ≥25% of tumor cells or in ≥25% or 100% of tumor-associated immune cells if the percentage of immune cells was >1% or ≤1%, respectively. If none of these criteria were met, PD-L1 status was considered negative.4

BSC=best supportive care; CI=confidence interval; PD-1=programmed death-1 receptor; PD-L1=programmed death ligand-1.

LONG-TERM EXPLORATORY ANALYSIS: Median overall survival (OS) from the start of first-line platinum-containing chemotherapy5

OS in all randomized patients, data cutoff June 4, 20215

Limitations:

  • This is an exploratory, post hoc analysis of OS data, calculated from the start of chemotherapy (based on investigator-reported data) to death 
  • This analysis only includes patients who did not progress on first-line platinum-containing chemotherapy and subsequently enrolled in the JAVELIN Bladder 100 trial 
  • Safety data are not available pre-randomization 
  • This analysis is inclusive of platinum-containing chemotherapy,* treatment-free interval, randomized study treatment with BAVENCIO + best supportive care (BSC) or BSC alone, and subsequent therapy
  • Therefore, no conclusions can be drawn from this OS analysis

Hazard ratio
(HR): 0.77

(95% CI: 0.64, 0.92)

29.7 months

(95% CI: 25.2, 34.0)
with BAVENCIO + BSC (n=350)

20.5 months

(95% CI: 19.0, 23.5)
with BSC alone (n=350)

OS from start of 1L chemotherapy by 1L chemotherapy regimen5
Data cutoff June 4, 20215

efficacy-table-desktop

*Patients were treated with platinum-containing chemotherapy for 4 to 6 cycles.5
The treatment-free interval was 4 to 10 weeks, per trial protocol.5
Stratified hazard ratio analyses are shown

BSC=best supportive care; CI=confidence interval; OS=overall survival.

Exploratory Subgroup Analysis

Long-term overall survival (OS) analysis, data cutoff June 4, 20214

Exploratory OS analyses of prespecified subgroups in all randomized patients4

Small patient numbers can be a limitation of subgroup analyses. These results are presented for descriptive purposes and cannot be interpreted as a demonstration of efficacy in any particular subgroup. The results show the variability of the observed treatment effect over several subgroups. No adjustments were made for multiple comparisons in the subgroup analyses.

Chart Showing Exploratory OS Analyses With BAVENCIO® (avelumab) + BSC and BSC Alone
Chart Showing Exploratory OS Analyses With BAVENCIO® (avelumab) + BSC and BSC Alone

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 this subgroup. OS was measured from time of randomization, after 4 to 6 cycles of platinum-based chemotherapy.
 

*HRs and CIs were calculated using a Cox proportional hazards model.
 

Stratified by best response to 1L chemotherapy (CR or PR vs SD) and metastatic disease site when initiating 1L chemotherapy (visceral vs nonvisceral).
 

Non-visceral includes patients with locally advanced disease in addition to patients with only non-visceral disease, including bone metastasis.
 

§Patients who switched platinum regimens while receiving 1L chemotherapy.

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National Comprehensive Cancer Network® (NCCN®) Recommendation

Avelumab (BAVENCIO) maintenance is the only NCCN CATEGORY 1 and PREFERRED immunotherapy option for both cisplatin-eligible and -ineligible patients with locally advanced or metastatic urothelial carcinoma (UC) that has not progressed on first-line platinum-containing chemotherapy.7

Category 1=Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Preferred intervention=Interventions that are based on superior efficacy, safety, and evidence; and, when appropriate, affordability.

View the Safety Information and Study Design

References: 1. Powles T, Park SH, Voog E, et al. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N Engl J Med. 2020;383(13):1218-1230. doi:10.1056/NEJMoa2002788 2. Bavencio. Prescribing information. EMD Serono, Inc.; 2023. 3. Grivas P, Park SH, Voog E, et al. Avelumab first-line maintenance therapy for advanced urothelial carcinoma: comprehensive clinical subgroup analyses from the JAVELIN Bladder 100 Phase 3 Trial. Eur Urol. 2023;S0302-2838(23)02708-2. doi:10.1016/j.eururo.2023.03.0302023. Online ahead of print. 4. 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;JCO2201792. doi:10.1200/JCO.22.01792. Online ahead of print. 5. Data on file. EMD Serono, Inc., Rockland, MA. 6. 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 [supplementary appendix]. J Clin Oncol. 2023;JCO2201792. doi:10.1200/JCO.22.01792. Online ahead of print. 7. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Bladder Cancer V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed January 23, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.