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Follow-up results from the phase III JAVELIN Bladder 100 trial provide more level 1 evidence demonstrating the efficacy and safety of first-line (1L) avelumab maintenance in patients with advanced urothelial carcinoma (aUC) who were progression-free after 1L platinum-containing chemotherapy.

The findings, reported in the, showed that 67 of 700 patients (19.5%) received ≥2 years of treatment. The overall survival (OS) rate was 49.8% in the avelumab arm versus 38.4% in the control arm. At 19.5 additional months from the initial analysis, progression-free survival (PFS) also remained significantly longer in the avelumab arm compared with controls.

"Longer-term results from JAVELIN Bladder 100 continue to show prolonged OS and PFS with avelumab 1L maintenance plus BSC [best supportive care] versus BSC alone in the overall population and across various subgroups," wrote Thomas Powles, MD, PhD, of Barts Cancer Institute and the University of London, and colleagues. "To our knowledge, JAVELIN Bladder 100 remains the only phase III trial to report significant improvement in OS in the 1L setting in patients with aUC since trials that established the efficacy of platinum-containing chemotherapy."

The data also revealed that the overall discontinuation rate due to treatment-related adverse events (TRAEs) was 10.2%, and that most TRAEs were low grade after 12 or more months. No new safety signals were identified.

This confirms the long-term safety profile of avelumab maintenance, "suggesting that long-term avelumab treatment is feasible and manageable," the authors wrote. "This is particularly important because patients with aUC tend to be older and have associated co-morbidities."

from the JAVELIN trial, reported in 2020, showed that 350 patients randomized to the avelumab arm had a median OS of 23.8 months compared with 15.0 months in the 350 controls. This led to the inclusion of avelumab 1L maintenance in guidelines for bladder cancer from both the and the .

The following Q&A discusses the details of the study. (The researchers did not respond to requests for comment, and the answers here are from the text of the report.)

What criteria were used for patient enrollment?

Eligible patients had locally advanced or metastatic urothelial carcinoma and were progression-free after 4-6 cycles of first-line chemotherapy with either cisplatin or carboplatin plus gemcitabine.

How was the patient population stratified?

Patients were randomly assigned 1:1 to either the avelumab arm or the control arm, stratified by visceral/nonvisceral metastatic disease site at chemotherapy initiation and response/stable disease with chemotherapy.

How did the new data on investigator-assessed PFS compare with the initial findings?

In the early analysis, the median investigator-assessed PFS was 5.5 months versus 2.1 months for controls. At 2 years, the PFS rates were 23.4% versus 7.1%, respectively.

In which subgroups was avelumab favored?

Although hazard ratios for geographic subgroups were similar in both study arms, our OS analyses showed that avelumab was favored across subgroups defined by chemotherapy regimen and best response to chemotherapy. Also, a pre-specified analysis showed that restricted mean survival time was 2.8 months longer for patients in the avelumab arm versus those who received supportive care only.

What did your analyses show about TRAEs in the avelumab arm?

Out of 344 patients treated with avelumab plus best supportive care, any-grade TRAEs occurred in 269 patients (78.2%) after 12 or more months. These included grade ≥3 TRAEs in 67 patients (19.5%), the most common of which were urinary tract infection, hypertriglyceridemia, and increases in lipase, alanine aminotransferase, and gamma-glutamyltransferase.

How many patients required second-line drug therapy?

A total of 158 out of 209 patients (75.6%) in the avelumab arm and 225 out of 275 (81.8%) in the control arm were taken off study therapy because of progressive disease. These patients received subsequent anticancer drug therapy, which consisted of a PD-1/PD-L1 inhibitor in 27 (12.9%) and 166 (60.4%) patients, respectively.

How do the rates of subsequent therapy compare with real-world practice?

OS was prolonged with avelumab even though the majority of control patients received subsequent anticancer drug therapy. In real-world clinical practice, only 30-40% of patients are able to receive . And while more patients may receive subsequent therapy in the maintenance setting, a significant do not, even in studies in which crossover is available.

Read the study here and expert commentary about it here.