Long-Term JAVELIN Bladder 100 Data Support Avelumab Maintenance in Advanced Urothelial Carcinoma

Shilpa Gupta, MD

First-line avelumab (Bavencio) maintenance therapy prolonged survival in patients with advanced urothelial carcinoma, regardless of response to first-line chemotherapy, according to findings from an exploratory subgroup analysis of the phase 3 JAVELIN Bladder 100 trial (NCT02603432) that were presented at the 2023 American Urological Association Annual Meeting.¹

This response was also seen despite a higher proportion of patients in the BSC alone arm receiving subsequent therapy.

“These findings further support avelumab first-line maintenance as the standard of care for all patients with locally advanced or metastatic urothelial cancer that has not progressed with first-line platinum-containing chemotherapy,” Shilpa Gupta, MD, director of genitourinary medical oncology at Taussig Cancer Institute and co-leader of the Genitourinary Oncology Program at Cleveland Clinic, said during her presentation.

In the exploratory analysis, investigators evaluated survival by subgroups that were defined by response to first-line chemotherapy after ≥2 years of follow-up, including complete response (CR; n = 179), partial response (PR = 326), or stable disease (SD; n = 195).

Median follow-up in both arms was ≥38 months after the data cut-off of June 4, 2021.

Across all patients who had a CR, PR, or SD to frontline chemotherapy, OS PFS were prolonged with the addition of avelumab.

Among patients with a CR after first-line chemotherapy, treatment was ongoing in 13.3% of patients with the addition of avelumab maintenance (n = 90), vs 6.7% in the control arm (n = 89). Median OS was 39.8 months (95% CI, 28.5-not evaluable [NE]) with avelumab, compared with 26.8 months (95% CI, 18.5-33.6), reducing the risk for death by 28% (HR, 0.72; 95% CI, 0.482-1.076). Similarly, median PFS was superior with the addition of the checkpoint inhibitor (9.5 months [95% CI, 5.7-16.6] vs 5.1 months [95% CI, 3.0-5.7]; HR, 0.58; 95% CI, 0.410-0.817).

Among patients with a PR after first-line chemotherapy, treatment was ongoing in 12.9% of patients in the avelumab arm (n = 163) and 0.6% in the control arm (n = 163). Median OS was 19.2 months (95% CI, 16.0-23.8) and 12.8 months (95% CI, 10.3-14.8), respectively, reducing the risk for death by 30% (HR, 0.70; 95% CI, 0.541-0.914). Median PFS was 3.8 months in the avelumab arm (95% CI, 3.7-5.6), vs 1.9 months in the control arm (95% CI, 1.9-2.1), reducing the risk for disease progression or death by 53% (HR, 0.47; 95% CI, 0.367-0.607).

Among patients with SD after first-line chemotherapy, treatment was ongoing in 10.3% of the avelumab arm (n = 97) and 3.1% of the control arm (n = 98). Median OS was 22.3 months (95% CI, 18.2-28.8) and 14.0 months (95% CI, 10.6-19.6), respectively, reducing the risk for death by 16% (HR, 0.84; 95% CI, 0.596-1.188). Median PFS was 5.6 months (95% CI, 3.7-7.5), vs 2.0 months (95% CI, 1.9-3.6), respectively (HR, 0.59; 95% CI, 0.421-0.816).

More patients in the BSC alone arm, compared with the avelumab arm, received a subsequent second-line anticancer drug therapy among patients with a CR (74.2% vs 50.0%, respectively), PR (71.8% vs 58.3%), or SD (70.4% vs 46.4%).

Long-term safety was consistent with previous findings of avelumab maintenance, including the frequency of adverse events (AEs) and treatment-related AEs, according to Gupta. However, a higher proportion of patients who experienced a CR (23.3%) reported an AE that led to treatment discontinuation, compared with patients who had a PR (10.0%) or SD (12.8%).

Phase 3 JAVELIN Bladder 100 Trial

In the phase 3 trial, investigators randomized 700 patients with unresectable locally advanced or metastatic urothelial cancer who did not have disease progression with first-line chemotherapy (which included 4 to 6 cycles of gemcitabine plus cisplatin or carboplatin) to receive BSC with (n = 350) or without (n = 350) maintenance avelumab.2 Patients were treated until progressive disease, unacceptable toxicity, or study withdrawal.

OS, among the overall population and those with PD-L1-positive tumors, served as the primary end point. Secondary end points included PFS and safety.

The 1-year OS rate was 71.3% with avelumab, compared with 58.4% with BSC alone. Similarly, median OS was superior with the checkpoint inhibitor (21.4 months vs. 14.3 months), reducing the risk for death by 31% (HR, 0.69; 95% CI, 0.56-0.86; P = .001).

Maintenance therapy with avelumab also reduced the risk for progression or death by 38% (HR, 0.62; 95% CI, 0.52-0.75), with a median PFS of 3.7 months vs 2.0 months in the BSC alone group.

Any grade AEs occurred in 98% and 77.7% of patients in the avelumab and control arms, respectively, including 47.4% and 25.2% that were grade 3 or higher.

“Results from this trial led to the approval of avelumab first-line maintenance in various countries worldwide,” Gupta said. “Avelumab first-line maintenance is now recommended as the standard of care in international treatment guidelines based on level 1 evidence.”

References

1. Valderrama B, Powles T, Sridhar S, et al. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): long-term outcomes from JAVELIN Bladder 100 in subgroups defined by response to 1L chemotherapy. J Urol. 2023;209(4):e244. doi:10.1097/JU.0000000000003240.10.
2. Powles T, Park SH, Voog E, et al. Avelumab maintenance therapy for advanced or metastatic urothelial carcinoma. N Engl J Med. 2020;383(13):1218-1230. doi:10.1056/NEJMoa2002788.