In the phase III JAVELIN Bladder 100 trial reported in The New England Journal of Medicine, Thomas Powles, MD, PhD, and colleagues found that maintenance treatment with avelumab plus best supportive care significantly improved overall survival vs best supportive care alone among patients whose disease had not progressed on first-line platinum-based chemotherapy.

The trial supported the June 2020 U.S. Food and Drug Administration approval of avelumab for maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy.

Thomas Powles, MD, PhD

Study Details

In the open-label trial, 700 patients from sites in 29 countries were randomly assigned between May 2016 and June 2019 to receive best supportive care with (n = 350) or without (n = 350) avelumab at 10 mg/kg every 2 weeks. Patients had unresectable locally advanced or metastatic urothelial cancer without disease progression on first-line chemotherapy consisting of four to six cycles of gemcitabine plus cisplatin or carboplatin. The primary endpoint was overall survival in the overall population and among patients with PD-L1–positive tumors.

Patients were classified as having PD-L1–positive status if one the following criteria were met:

• ≥ 25% of tumor cells stained for PD-L1
• ≥ 25% of immune cells stained for PD-L1 if > 1% of the tumor area contained immune cells
• 100% of immune cells stained for PD-L1 if no more than 1% of the tumor area contained immune cells.

Among patients evaluated for PD-L1 status, tumors were classified as PD-L1–positive in 189 (57.6%) of 328 patients in the avelumab group and in 169 (56.3%) of 300 in the control group.

Overall Survival

Median follow-up for overall survival was > 19 months in both groups. Among all patients, median overall survival was 21.4 months (95% confidence interval [CI] = 18.9–26.1 months) in the avelumab group vs 14.3 months (95% CI = 12.9–17.9 months) in the control group (stratified hazard ratio [HR] = 0.69, 95% CI = 0.56–0.86; P = .001). Rates at 1 year were 71.3% vs 58.4%.

In the PD-L1–positive population, median overall survival was not reached (95% CI = 20.3 months–not estimable) in the avelumab group vs 17.1 months (95% CI = 13.5–23.7 months) in the control group (HR = 0.56, 95% CI = 0.40–0.79; P < .001). Rates at 1 year were 79.1% vs 60.4%.

Median progression-free survival was 3.7 months (95% CI = 3.5–5.5 months) in the avelumab group vs 2.0 months (95% CI = 1.9–2.7 months) in the control group (HR = 0.62, 95% CI = 0.52–0.75) in the overall population. In the PD-L1–positive population, median progression-free survival was 5.7 months (95% CI = 3.7–7.4 months) in the avelumab group and 2.1 months (95% CI = 1.9–3.5 months) in the control group (HR = 0.56, 95% CI = 0.43–0.73).

Adverse Events

The incidence of adverse events from any cause was 98.0% in the avelumab group and 77.7% in the control group. Adverse events of ≥ grade 3 occurred in 163 patients (47.4%) in the avelumab group vs 87 (25.2%) in the control group, with the most common in the avelumab group including urinary tract infection (4.4%), anemia (3.8%), fatigue (1.7%), and hematuria (1.7%). Adverse events in the avelumab group led to treatment discontinuation in 41 patients (11.9%).

The investigators concluded, “Maintenance avelumab plus best supportive care significantly prolonged overall survival as compared with best supportive care alone among patients with urothelial cancer who had disease that had not progressed with first-line chemotherapy.”

Disclosure: The study was funded by Pfizer and Merck. For full disclosures of the study authors, visit nejm.org.