Survival Data Supports Use of Avelumab in Advanced Urothelial Carcinoma

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Avelumab (Bavencio) first-line maintenance with best supportive care (BSC) led to significantly prolonged overall survival (OS) and progression-free survival (PFS) vs BSC alone in patients with advanced urothelial carcinoma (UC) who were progression-free after 4-6 cycles of first-line platinum-based chemotherapy and had an interval of 4-10 weeks between the end of chemotherapy and the start of maintenance.¹

Findings from a post hoc analysis of OS and PFS from the JAVELIN Bladder 100 trial (NCT02603432) support the use of this combination as a standard of care for patients with UC. In the study, hazard ratios (HRs) for OS with avelumab first-line maintenance vs BSC alone across all subgroups defined by the duration of first-line chemotherapy (0.63-0.79) and in patients who had received 4 or 6 cycles of chemotherapy (0.69 and 0.66, respectively) were generally consistent with the HR in the overall population of 0.69. Among patients given 5 cycles of chemotherapy, the HR was 0.98. However, this subgroup was small and made up of only 16% of patients.

Looking at safety, the safety profile of avelumab first-line maintenance was similar across all subgroups and was consistent with the results from prior studies evaluating avelumab as a monotherapy.

In the study, 700 patients with advanced UC were randomized to receive avelumab with BSC (n = 350) or BSC alone (n = 350). Patients were eligible for enrollment if they had histologically confirmed unresectable locally advanced or metastatic UC, no disease progression with 4-6 cycles of gemcitabine and cisplatin and/or gemcitabine and carboplatin before enrollment, and an ECOG performance status of 0 or 1.² Baseline characteristics of those enrolled in the study were generally balanced across subgroups.

Avelumab was given to patients at a dose of 10 mg/kg given via intravenous infusion once every 2 weeks.¹ BSC was administered based on patient needs and investigator clinical judgment. Patients continued treatment until confirmed progression, unacceptable toxicity, patient withdrawal, or any other prespecified criterion for discontinuation occurred.The primary end point evaluated in the study was OS, and secondary end points included PFS and safety.

At a data cutoff date of October 21, 2019, the median follow-ups were 19.6 months and 19.2 months in the avelumab and control arms, respectively. In the <Q1 subgroup which consisted of 171 patients, the median OS was 18.9 months with avelumab vs 13.0 months among patients in the control arm (HR, 0.65; 95% CI, 0.42-1.02). Here, the median PFS was 3.5 months in the experimental arm vs 1.9 months in the control arm, respectively (HR, 0.71; 95% CI, 0.49-1.02).

In the Q1-Q2 subgroup of 145 patients, the median OS was 19.9 months with avelumab and BSC vs 15.5 months with BSC alone (HR, 0.79; 95% CI, 0.50-1.27), and the median PFS was 5.6 months and 1.9 months (HR, 0.57; 95% CI, 0.37-0.86), respectively. Among the 211 patients included in the Q2-Q3 subgroup, the median OS with avelumab and BSC vs BSC alone was 19.2 months and 14.3 months (HR, 0.74; 95% CI, 0.50-1.10), and the median PFS was 3.6 months and 1.9 months (HR, 0.68; 95% CI, 0.49-0.94), respectively.

Then in the >Q3 subgroup, which included 171 patients, the median OS was 24.0 months and 17.9 months (HR, 0.63; 95% CI, 0.39-1.00). The median PFS in this subgroup was 5.6 months with the addition of avelumab and 3.5 months with BSC alone (HR, 0.55; 95% CI, 0.37-0.80), respectively. The 4-cycle subgroup of 251 showed a median OS of 19.9 months with avelumab vs 13.7 months with the control (HR, 0.69; 95% CI, 0.48-1.00), and the median PFS was 3.8 months vs 2.0 months, respectively (HR, 0.59; 95% CI, 0.43-0.80).

The median OS in the 5-cycle subgroup of 113 patients was 19.9 months and 17.8 months with the experimental and control arms (HR, 0.98; 95% CI, 0.57-1.71), and the median PFS was 2.4 months and 2.1 months (HR, 0.77;95% CI, 0.48-1.22), respectively. Lastly, in the 6-cycle subgroup of298 patients, the median OS was 24.0 months and 14.0 months (HR, 0.66; 95% CI, 0.47-0.92), and the median PFS was 3.7 months and 1.9 months (HR, 0.60; 95% CI, 0.45-0.79), respectively.

For safety, grade ≥3 treatment-emergent adverse events (AEs) were seen in 42%-62% of patients treated with the addition of avelumab arm, including grade ≥3 treatment-related AEs (TRAEs) in 15%-19%, and any-grade immune-related AEs (irAEs) in 25%-36% in subgroups defined by the duration of first-line chemotherapy. Among those in the subgroups defined by cycles of first-line chemotherapy, grade ≥3 AEs were observed in 45%-54% of patients treated with avelumab plus BSC, including grade ≥3 TRAEs in 7.4%–19%, and any-grade irAEs occurred in 28%-34%.

Prospective trials are warranted to confirm these findings.

REFERENCES:

1. Sridhar SS, Powles T, Climent Durán MÁ, et al. Avelumab first-line maintenance for advanced urothelial carcinoma: analysis from JAVELIN bladder 100 by duration of first-line chemotherapy and interval before maintenance [published online ahead of print, 2023 Sep 13]. Eur Urol. 2023;S0302-2838(23)03020-8. doi:10.1016/j.eururo.2023.08.001

2. A study Of avelumab in patients with locally advanced or metastatic urothelial cancer (JAVELIN Bladder 100). ClinicalTrials.gov. Accessed June 6, 2023. Accessed October 16, 2023. https://tinyurl.com/zes9pr6v