Clinical trialPhase 3Bladder cancer

Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma

N Engl J Med · 2020700 patients

Powles T, Park SH, Voog E, et al. N Engl J Med. 2020. 383:1218-1230

A newer report of this study has been published: Avelumab First-Line Maintenance for Advanced Urothelial Carcinoma: Results From the JAVELIN Bladder 100 Trial After ≥2 Years of Follow-Up (2023)

Study type: Clinical trial
Study name: JAVELIN Bladder 100
Phase: Phase 3
Design: Randomised, open-label, multicentre trial (1:1 randomisation)
Sample size: 700 patients
Source: N Engl J Med · 2020
Trial registration: NCT02603432

In plain words

If advanced bladder cancer is kept under control (does not grow) with the first chemotherapy, maintenance treatment with the immunotherapy drug avelumab can be started instead of "watch and wait". In this study, this lengthened life on average from about 14 months to 21 months. Today in many countries the preferred first treatment is enfortumab vedotin + pembrolizumab, but for patients who receive platinum chemotherapy, maintenance avelumab remains a standard option.

Key results

21.4 vs 14.3 months

Median overall survival (overall population)

HR for death 0.69 (95% CI 0.56–0.86); P=0.001

71.3% vs 58.4%

1-year overall survival

In the PD-L1-positive population: 79.1% vs 60.4%; HR 0.56; P<0.001

3.7 vs 2.0 months

Median progression-free survival (overall population)

HR 0.62 (95% CI 0.52–0.75)

47.4% vs 25.2%

Grade 3 or higher adverse events (all causes)

Drugs in this study:Carboplatin (Paraplatin)Cisplatin (Platinol)Gemcitabine (Gemzar)

Dose and schedule cards

Gemcitabine + cisplatin or carboplatin, followed by avelumab maintenance (JAVELIN Bladder 100)

First-line platinum-based chemotherapy (carboplatin if cisplatin-ineligible); avelumab in patients without progression after 4 to 6 cycles (response or stable disease)On the page “Bladder cancer” · Advanced or metastatic disease: first line

First-line platinum-based chemotherapy (carboplatin if cisplatin-ineligible); avelumab in patients without progression after 4 to 6 cycles (response or stable disease)

Drug	Dose	Route	Schedule
Chemotherapy: 4 to 6 cycles of 21 days
Gemcitabine	1000 mg/m²	IV	Days 1 and 8
Cisplatin or carboplatin	Cisplatin 70 mg/m² or carboplatin AUC 4.5 or 5	IV	Day 1
Maintenance
Avelumab	800 mg (10 mg/kg in the trial)	IV over 60 minutes	Every 2 weeks; start 4 to 10 weeks after the last dose of chemotherapy

Cycle length: Chemotherapy every 21 days; avelumab every 14 days
Duration: Avelumab until progression or unacceptable toxicity

Chemotherapy doses per the EV-302 control arm in the FDA label; avelumab per the label and the trial. Avelumab premedication: an antihistamine and acetaminophen before the first 4 infusions, then as needed.

On the page “Bladder cancer” · Advanced or metastatic disease: first line

Maintenance avelumab

After 4 to 6 cycles of platinum chemotherapy without progressionCycle length: Every 14 daysOn the page “Gemcitabine-cisplatin in bladder cancer and maintenance avelumab”

After 4 to 6 cycles of platinum chemotherapy without progression

Drug	Dose	Route	Schedule
Avelumab	10 mg/kg (or 800 mg)	IV	Day 1

Cycle length: Every 14 days
Duration: Until progression

As in JAVELIN Bladder 100; antihistamine and paracetamol premedication for the first 4 doses.

Dose source:.

On the page “Gemcitabine-cisplatin in bladder cancer and maintenance avelumab”

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Avelumab + best supportive care

Avelumab 10 mg/kg as a 1-hour IV infusion every 2 weeks (4-week cycles) with best supportive care, until confirmed progression or unacceptable toxicity (continuation beyond progression was allowed in stable patients with clinical benefit). Recommended flat dose in the FDA label: 800 mg over 60 minutes every 2 weeks, with antihistamine and paracetamol (acetaminophen) premedication before the first 4 infusions.

2Best supportive care alone (control)

Best supportive care without active anticancer treatment (palliative radiotherapy of isolated lesions was allowed).

Source of the regimen details: FDA label for BAVENCIO (DailyMed; trial dose 10 mg/kg every 2 weeks and recommended dose 800 mg) and ClinicalTrials.gov NCT02603432

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

700 patients with unresectable locally advanced or metastatic urothelial carcinoma (stage IV at the start of chemotherapy; measurable disease before chemotherapy) whose disease had not progressed with 4 to 6 cycles of first-line gemcitabine + cisplatin and/or carboplatin (complete or partial response or stable disease); treatment started 4 to 10 weeks after the last chemotherapy dose. Prior immunotherapy, neoadjuvant/adjuvant treatment within 12 months and autoimmune disease were exclusion criteria.

Endpoints

Primary endpoint: overall survival in all randomised patients and in patients with PD-L1-positive tumours. Secondary endpoints: progression-free survival and safety.

Safety and side effects

All-cause adverse events occurred in 98.0% of the avelumab group and 77.7% of the control group; grade 3 or higher events in 47.4% and 25.2%, respectively. Immune-mediated adverse events and infusion reactions are known adverse effects of avelumab (details in the full text).

Clinical significance and place in guidelines

On 30 June 2020 the FDA approved avelumab for maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy. The EAU 2025 guideline recommends, when enfortumab vedotin is contraindicated or unavailable, platinum-based combination chemotherapy followed by maintenance avelumab in patients with at least stable disease (strong recommendation).

Limitations

Open-label design; only patients whose disease had not progressed on chemotherapy were enrolled (patients who progress during chemotherapy do not benefit from this strategy); the study was done before the era of first-line enfortumab vedotin + pembrolizumab.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.