You are about to leave this site and are being redirected to another site. Would you like to leave this site?

 

First-line maintenance treatment of urothelial carcinoma
BAVENCIO® (avelumab) is indicated for the maintenance
treatment of patients with locally advanced or metastatic
urothelial carcinoma (UC) that has not progressed with
first-line platinum-containing chemotherapy.

The FIRST and ONLY immunotherapy
approved in the first-line
maintenance setting




 

 

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

Study design

 

  • Stratified by best response to chemotherapy (CR/PR [72%] vs SD [28%] per RECIST v1.1) and site of metastasis (visceral [55%] vs nonvisceral, including bone metastasis [45%]) assessed at the time of initiating first-line platinum-containing chemotherapy1
  • First-line chemotherapy regimens included prior gemcitabine plus cisplatin (56%), prior gemcitabine plus carboplatin (38%), and prior gemcitabine plus cisplatin and gemcitabine plus carboplatin (6%)
  • Administration of BAVENCIO was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator
  • Assessment of tumor status was performed at baseline, 8 weeks after randomization, then every 8 weeks up to 12 months after randomization, and every 12 weeks thereafter until documented confirmed disease progression based on BICR assessment per RECIST v1.1

*BSC was administered as deemed appropriate by the treating physician, and could include treatment with antibiotics, nutritional   support, and other patient management approaches with palliative intent (excludes active antitumor therapy).1
PD-L1 expression was assessed in tumor samples using the VENTANA PD-L1 (SP263) assay.1
BICR=blinded independent central review; CR=complete response; ECOG PS=Eastern Cooperative Oncology Group (ECOG) Performance Status; PD-L1=programmed death ligand-1; PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumors; SD=stable disease.



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

BAVENCIO + best supportive care (BSC) demonstrated superior overall survival (OS) vs BSC alone

All randomized patients (major efficacy outcome measure)

 

 

*P-value based on stratified log-rank.

 CI=confidence interval; PD-1=programmed death-1 receptor; PD-L1=programmed death ligand-1.

  • OS was measured post-randomization (after chemotherapy)
  • 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 BSC arm received another PD-1/PD-L1 checkpoint inhibitor as subsequent therapy vs 6% of patients in the BAVENCIO + BSC arm

OS in patients with PD-L1-positive tumors (major efficacy outcome measure)

  • BAVENCIO + BSC demonstrated statistically significant improvement in OS vs BSC alone in patients with PD-L1-positive tumors (n=358, 51%); the hazard ratio was 0.56 (95% CI: 0.40, 0.79; 2-sided P-value <0.001)

OS in patients with PD-L1-negative tumors (exploratory analysis)

  • In patients with PD-L1-negative tumors (n=271, 39%), the OS hazard ratio was 0.85 (95% CI: 0.62, 1.18)

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

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 firstline platinum-containing chemotherapy (N=689)1

BAVENCIO—adverse reaction profile

  • A fatal adverse reaction (sepsis) occurred in one (0.3%) patient receiving BAVENCIO + best supportive care (BSC) alone
  • Serious adverse reactions occurred in 28% of patients receiving BAVENCIO plus BSC. Serious adverse reactions in ≥1% of patients included urinary tract infection (including kidney infection, pyelonephritis, and urosepsis) (6.1%), pain (including abdominal, back, bone, flank, extremity, and pelvic pain) (3.2%), acute kidney injury (1.7%), hematuria (1.5%), sepsis (1.2%), and infusion-related reaction (1.2%)
  • Thirty-one (9%) patients treated with BAVENCIO + BSC received an oral prednisone dose equivalent to ≥40 mg daily for an immune-mediated adverse reaction
  • Patients received premedication with an antihistamine and acetaminophen prior to each infusion. Infusion-related reactions occurred in 10% of patients treated with BAVENCIO + BSC (Grade 3: 0.9%)

Adverse reactions (≥10%) of patients receiving BAVENCIO + BSC

 

*Fatigue is a composite term that includes fatigue, asthenia, and malaise.
Musculoskeletal pain is a composite term that includes musculoskeletal pain, back pain, myalgia, and neck pain.
Rash is a composite term that includes rash, rash maculo-papular, erythema, dermatitis acneiform, eczema, erythema multiforme,   rash erythematous,  rash macular, rash papular, rash pruritic, drug eruption, and lichen planus.
§Urinary tract infection is a composite term that includes urinary tract infection, urosepsis, cystitis, kidney infection,   pyuria,pyelonephritis, bacteriuria, pyelonephritis acute, urinary tract infection bacterial, and Escherichia urinary tract infection.
llCough is a composite term that includes cough and productive cough.

Discontinuation rates due to an adverse reaction

  • In the BAVENCIO + best supportive care (BSC) arm (n=344), permanent discontinuation due to an adverse reaction occurred in 12% of patients
    • Adverse reactions resulting in permanent discontinuation of BAVENCIO in >1% of patients were myocardial infarction (including acute myocardial infarction and troponin T increased) (1.5%) and infusion-related reaction (1.2%)

Dose interruptions due to an adverse reaction

  • In the BAVENCIO + BSC arm (n=344), dose interruptions due to an adverse reaction, excluding temporary interruptions of BAVENCIO infusions due to infusion-related reactions, occurred in 41% of patients
    • Adverse reactions leading to interruption of BAVENCIO in >2% of patients were urinary tract infection (including pyelonephritis) (4.7%) and blood creatinine increased (including acute kidney injury, renal impairment, and renal failure) (3.8%)

 

Selected laboratory abnormalities worsening from baseline occurring in ≥10% of patients receiving BAVENCIO + BSC

*Each test incidence is based on the number of patients who had both baseline and at least one on-study laboratory measurement available: BAVENCIO + BSC group (range: 339 to 344 patients) and BSC group (range: 329 to 341 patients).

National Comprehensive Cancer Network® (NCCN) Recommendation

Avelumab maintenance therapy (category 2A) is recommended as part of a preferred regimen as an option for first-line systemic therapy in patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.2

Category 2A=Based upon lower-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.

 

 

References: 1. Data on file. Rockland, Mass: EMD Serono, Inc. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Bladder Cancer V.6.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed July 17, 2020. To view the most recent and complete version of the guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content or its use or application and disclaims any responsibility for its use or application in any way.