Clinical trialPhase 3Bladder cancer

Avelumab First-Line Maintenance for Advanced Urothelial Carcinoma: Results From the JAVELIN Bladder 100 Trial After ≥2 Years of Follow-Up

J Clin Oncol · 2023700 patients

Powles T, Park SH, Caserta C, Valderrama BP, Gurney H, Ullén A, et al. J Clin Oncol. 2023. 41:3486-3492

Study type: Clinical trial
Study name: JAVELIN Bladder 100
Phase: Phase 3
Design: Randomised trial (1:1); update with at least 2 years of follow-up
Sample size: 700 patients
Source: J Clin Oncol · 2023
Trial registration: NCT02603432

In plain words

In patients whose advanced bladder cancer had been brought under control by platinum chemotherapy, continuing treatment with the immunotherapy drug avelumab still lowered the risk of death by about a quarter after more than 2 years of follow-up.

Key results

Hazard ratio 0.76

Overall survival (all patients)

0.63–0.91; P=0.0036 (two-sided)

38.0 and 39.6 months

Median follow-up

67 patients (19.5%)

Avelumab received for 2 years or more

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

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

Source of the regimen details: Full text of the paper (PMC10306435) and the FDA label for BAVENCIO (DailyMed)

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

Overall survival (primary endpoint), progression-free survival, safety and new analyses.

Safety and side effects

Among 344 patients receiving avelumab: all-cause adverse events 98.3% (grade 3 or higher 53.8%); treatment-related adverse events 78.2% (grade 3 or higher 19.5%). Among 118 patients treated for at least 12 months, treatment-related adverse events after 12 months occurred in 50.0% (grade 3 or higher 11.9%) and led to avelumab discontinuation in 10.2% and to one death (immune-mediated nephritis). Long-term safety was consistent with previous analyses.

Clinical significance and place in guidelines

This update confirmed the durability of the survival benefit of maintenance avelumab after platinum chemotherapy; the EAU guideline considers this strategy an alternative to EV + pembrolizumab when that combination is unavailable or contraindicated.

Limitations

Only patients whose disease had not progressed after chemotherapy were enrolled; the control group did not receive maintenance immunotherapy. Median overall survival is not reported in the abstract.

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.