First-Line Avelumab Maintenance Extends OS in Advanced Urothelial Carcinoma With Low Tumor Burden

First-line maintenance with avelumab (Bavencio) demonstrated efficacy and manageable toxicity in patients with advanced urothelial carcinoma and low tumor burden, according to findings from a post-hoc analysis of the phase 3 JAVELIN Bladder 100 trial (NCT02603432) that were presented at the 2024 ASCO Annual Meeting. These findings build on those from the primary analysis which had shown an improvement in overall survival (OS) and progression-free survival (PFS) with maintenance avelumab vs best supportive care (BSC) in patients whose disease had not progressed following frontline platinum-based chemotherapy.

At a data cutoff of June 4, 2021, and a median follow-up of over 38 months, median OS in patients who received avelumab with nonvisceral metastases (n = 159), lymph node–only disease (n = 51), and pelvic/retroperitoneal lymph node–only disease (n = 42) was 31.4 months (95% CI, 26.1-36.8), 31.9 months (95% CI, 26.1-44.5), and 31.2 months (95% CI, 23.8-44.5), respectively. In the BSC arm the median OS in patients with nonvisceral metastases (n = 159), lymph node–only disease (n = 51), and pelvic/retroperitoneal lymph node–only disease (n = 35) was 17.1 months (95% CI, 13.7-21.3), 22.7 months (95% CI, 16.5-not evaluable [NE]), and 20.2 months (95% CI, 13.7-NE), respectively.

Investigator-assessed PFS was also longer with avelumab vs BSC, respectively, at 9.0 months (95% CI, 5.7-12.6) vs 3.3 months (95% CI, 2.0-3.7) in patients with nonvisceral metastases, 8.7 months (95% CI, 5.4-24.7) vs 3.7 months (95% CI, 2.0-6.0) in those with lymph node–only disease, and 7.5 months (95% CI, 4.2-12.0) vs 3.7 months (95% CI, 1.9-5.7) in patients with pelvic/retroperitoneal lymph node–only disease.

“It was shown that adding maintenance immunotherapy with avelumab improved survival, becoming a new standard of care in the first line,” Joaquim Bellmunt, MD, PhD, presenting study author, said in an interview with OncLive.

In the interview, Bellmunt expanded on the utility and background of avelumab when given in the first-line maintenance setting following platinum-based chemotherapy and highlighted the outcomes from the primary and post-hoc analysis of the phase 3 JAVELIN Bladder 100 study.

Bellmunt is a senior physician and director of the Bladder Cancer Center at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School in Boston, Massachusetts.

OncLive: Please expand on the prior findings from JAVELIN Bladder 100.

Bellmunt: [The data from] JAVELIN Bladder 100, which were published in the New England Journal of Medicine with level 1 evidence of survival benefit, led to the approval of frontline avelumab maintenance in the management of metastatic bladder cancer. This trial randomly assigned patients who did not progress on platinum-based therapy to receive immunotherapy or observation.

Since this trial was published, 2 additional trials with level 1 evidence have been published. We have now 3 options for treating [patients with] metastatic bladder cancer in the first line.

What findings were shared from the study at the 2024 ASCO Annual Meeting?

With a medium follow-up of 38 months, we updated the benefits of adding avelumab maintenance [to treatment] in patients who did not progress on platinum-based therapy. In addition, we analyzed, now that the trial has long-term follow-up, the benefit of giving maintenance avelumab in patients with low tumor burden. Low tumor burden was defined as patients having either nonvisceral metastases, lymph node–only disease, or pelvic and retroperitoneal lymph node–only disease.

When we analyzed this group of patients with low tumor burden [we found] that the benefit of avelumab is [upheld]. We also saw that the median OS [surpassed] 31 months, meaning that patients with a low tumor burden see more benefit when receiving maintenance [avelumab]. The median OS in the overall group was 21 months; it went up to 24 with follow-up, and now we see this median OS of 31 months [in patients with low tumor burden].

What are the clinical implications of these findings?

For the United States [it] does not have huge implications, because we have enfortumab vedotin-ejfv [Padcev] plus pembrolizumab [Keytruda] which has been widely used [since its approval]. However, there are other countries that don’t have access to enfortumab vedotin plus pembrolizumab, such as several countries in Europe.

We want to know if the other options work within a selected patient population. These data provide support for the use of maintenance [avelumab] in patients with low tumor burden, meaning that these patients [can receive] this treatment if they don’t have access to the preferred first-line therapy of enfortumab vedotin plus pembrolizumab.

Reference

Bellmunt J, Powles T, Park SH, et al. Avelumab first-line maintenance (1LM) for advanced urothelial carcinoma (aUC): long-term outcomes from JAVELIN Bladder 100 in patients (pts) with low tumor burden. J Clin Oncol. 2024;42(suppl 16):4566. doi:10.1200/JCO.2024.42.16_suppl.4566