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ASCO GU 2025: Real-World Effectiveness and Safety of Avelumab First-Line Maintenance Treatment in Patients with Locally Advanced or Metastatic Urothelial Carcinoma: Second Interim Analysis of the AVENUE Study.

(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Annual Symposium held in San Francisco, CA between February 13–15, 2025 was host to a urothelial carcinoma poster session. Dr. Peter J. Goebell presented the 2nd interim analysis of the AVENUE study evaluating the real-world effectiveness and safety of avelumab 1st line (1L) maintenance treatment in patients with locally advanced or metastatic urothelial carcinoma (la/mUC).


Avelumab 1L maintenance is recommended for patients with la/mUC without disease progression after 1L platinum-based chemotherapy, based on results from the JAVELIN Bladder 100 trial.1

In the JAVELIN-100 trial, after ≥2 years of follow-up in the avelumab + best supportive care (BSC) vs BSC alone arms, the median overall survival (OS) from the start of maintenance was 23.8 vs 15 months (hazard ratio [HR]: 0.76, 95% CI: 0.63-0.91; p=0.0036) and the median progression-free survival (PFS) was 5.5 vs 2.1 months (HR: 0.54, 95% CI: 0.46–0.64; p<0.0001), respectively. Additionally, the long-term safety of avelumab 1L maintenance was also demonstrated.1 Real-world studies performed in several countries, including France, Italy, the US, and Japan, have reported that outcomes with avelumab IL maintenance were generally consistent with clinical trial findings.2,3

AVENUE is a real-world study evaluating the effectiveness and safety of avelumab IL maintenance treatment in routine clinical practice in several countries, namely Germany, Spain, Switzerland, and Russia. Previous results from the first interim analysis showed the acceptable safety profile of avelumab IL maintenance in a heterogeneous real-world population.

Here, Dr. Goebell reported initial effectiveness data and updated baseline and safety data from the second interim analysis.

AVENUE is an ongoing, prospective, noninterventional study in patients with la/mUC without disease progression after 1L platinum-based chemotherapy and planned avelumab treatment.

Initiation of avelumab 1L maintenance is decided by the treating physician prior to enrollment per local approval. Patients are followed for 36 months from the start of avelumab treatment (index date). No study-specific visits are required, and patients are assessed and followed up per standard clinical practice. Data are collected by investigators using a study-specific electronic case report form. 

The primary objective is to evaluate the OS rates at 12, 24, and 36 months. Secondary objectives include assessments of median OS, median PFS, tumor response, and safety. Disease control rate was defined as the percentage of patients who had complete response, partial response, or stable disease as their best response within 6 months from the start of avelumab treatment.

By the data cutoff (May 9, 2024), 177 patients had received avelumab IL maintenance, and the median follow-up was 10 months. The patient and disease characteristics are shown in the table below. The median age was 70 years. Most patients were male (78%) and had an Eastern Cooperative Oncology Group performance status of 0 or 1 (89.3%). 1L platinum-based chemotherapy regimen was gemcitabine + cisplatin in 61% of patients (split-dose cisplatin in 8.5%), gemcitabine + carboplatin in 36.2%, and switch/other in 3.4%.
By the data cutoff (May 9, 2024), 177 patients had received avelumab IL maintenance, and the median follow-up was 10 months. The patient and disease characteristics are shown in the table below. The median age was 70 years. Most patients were male (78%) and had an Eastern Cooperative Oncology Group performance status of 0 or 1 (89.3%). 1L platinum-based chemotherapy regimen was gemcitabine + cisplatin in 61% of patients (split-dose cisplatin in 8.5%), gemcitabine + carboplatin in 36.2%, and switch/other in 3.4%.
The median time to avelumab maintenance initiation after chemotherapy was 6.1 weeks. The median duration of avelumab maintenance treatment was 6 months. The 6-and 12-month OS rates were 80.6% (95% CI: 73.9–85.7%) and 69.1% (95% CI: 61.1-75.7%), respectively. The median OS was not reached (95% CI: 17 months–not estimable).The median time to avelumab maintenance initiation after chemotherapy was 6.1 weeks. The median duration of avelumab maintenance treatment was 6 months. The 6-and 12-month OS rates were 80.6% (95% CI: 73.9–85.7%) and 69.1% (95% CI: 61.1-75.7%), respectively. The median OS was not reached (95% CI: 17 months–not estimable).  
The median PFS was 5.8 months (95% CI: 4.6–9.1 months). The 6- and 12-month PFS rates were 50% (95% CI: 42.1–57.3%) and 33.1% (95% CI: 25.2–41.2%), respectively.The median PFS was 5.8 months (95% CI: 4.6–9.1 months). The 6- and 12-month PFS rates were 50% (95% CI: 42.1–57.3%) and 33.1% (95% CI: 25.2–41.2%), respectively.
The objective response rate and disease control rate (assessed up to 6 months in patients with available data) with avelumab maintenance was 22% (95% CI: 15.6–29.3%) and 67% (95% CI: 58.8–74.3%), respectively.

Treatment-related adverse events (TRAEs) occurred in 102 patients (57.6%), including grade ≥3 TRAEs in 28 patients (15.8%).Treatment-related adverse events (TRAEs) occurred in 102 patients (57.6%), including grade ≥3 TRAEs in 28 patients (15.8%).
The most common any-grade TRAEs were fatigue (9.6%), hyperthyroidism (5.1%), pruritus (4.5%), and diarrhea (4%).The most common any-grade TRAEs were fatigue (9.6%), hyperthyroidism (5.1%), pruritus (4.5%), and diarrhea (4%).
Grade ≥3 immune related AEs and infusion-related reactions occurred in 11 (6.2%) and 6 patients (3.4%), respectively. At last follow-up, 51 patients (28.8%) remained on avelumab treatment. The most common reasons for avelumab discontinuation were disease progression (72 [57.1%]), death (21 [16.7%]), and an AE (17 [13.5%]).

Overall, 61 patients (34.5%) received second-line treatment (48.4% of discontinuing patients), including 39 (22%) who received enfortumab vedotin. 15 patients (8.5%) received third-line treatment, including 4 (2.3%) who received enfortumab vedotin.
Overall, 61 patients (34.5%) received second-line treatment (48.4% of discontinuing patients), including 39 (22%) who received enfortumab vedotin. 15 patients (8.5%) received third-line treatment, including 4 (2.3%) who received enfortumab vedotin.
Dr. Goebell concluded as follows:

  • Previous results from the first interim analysis of the prospective, real-world AVENUE study showed that avelumab first-line (1L) maintenance had an acceptable safety profile in a heterogeneous population of patients with locally advanced or metastatic urothelial carcinoma (la/mUC) who were progression free following platinum-based chemotherapy in Germany, Spain, Switzerland, and Russia.
  • Results from the second interim analysis reported here demonstrate the effectiveness and confirm the acceptable safety profile of avelumab 1L maintenance treatment in routine clinical practice.
  • Results are generally consistent with findings from the JAVELIN Bladder 100 phase III trial and other real-world studies
  • Overall, results from the AVENUE study provide further clinical evidence supporting the use of avelumab 1L maintenance treatment as a standard of care in patients with advanced urothelial carcinoma that has not progressed with 1L platinum-based chemothera.py

Presented by: Peter J. Goebell, MD, PhD, Department of Urology and Pediatric Urology, University Hospital Erlangen, Erlangen, Germany

Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025. 

References:
  1. 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.
  2. Barthélémy P, Thibault C, Flechon A, et al. Real-world Study of Avelumab First-line Maintenance Treatment in Patients with Advanced Urothelial Carcinoma in France: Overall Results from the Noninterventional AVENANCE Study and Analysis of Outcomes by Second-line Treatment. Eur Urol Oncol. 2024 [Epub ahead of print].
  3. Grivas P, Barata P, Moon H, et al. Avelumab First-Line Maintenance for Locally Advanced or Metastatic Urothelial Carcinoma: Results From the Real-World US PATRIOT-II Study. Clin Genitourin Cancer. 2024; 22(16):102238.