ASCO GU 2022: First Line Avelumab in PD-L1+ve Metastatic or Locally Advanced Urothelial Cancer Patients Unfit for Cisplatin: The ARIES Trial

( On the second day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022, the Rapid Abstract Session highlighted key abstract in urothelial carcinoma, including work by Dr. Iacovelli and colleagues who examined first-line avelumab in patients with PD-L1+ve metastatic or locally advanced urothelial cancer (aUC) who are unfit for cisplatin. Avelumab IS approved as maintenance therapy after platinum-based first-line (1L) therapy for patients with aUC based on data from the phase III JAVELIN Bladder 100 trial.

In this study, the authors performed a single-arm, multi-site, open-label phase II trial (ARIES) among patients with aUC who were deemed unfit for cisplatin on the basis of at least one of: ECOG-PS = 2, CrCl < 60 mL/min, grade ≥2 peripheral neuropathy/hearing loss, or disease progression within 6-mos before the end of neoadjuvant or adjuvant chemotherapy. Further, patients had to have not previously received chemo for aUC and have PD-L1≥5% (SP263) based on central assessment.


Once enrolled, patients received avelumab 10 mg/Kg IV Q2W until progression, unacceptable toxicity, and withdrawal, whichever occurred first. The primary endpoint was the 1-year overall survival with key secondary endpoints including median-OS, -PFS, ORR, and safety.

Among 198 eligible cisplatin-unfit patients who underwent PD-L1 testing, 71 (35.6%) were found to be positive. Among these enrolled patients (N = 71), the median age was 75 years, 35 (49.3%) had visceral disease, and 22 (31.0%) had ECOG-PS = 2. Notably, 50 (70.4%) had CrCl < 60 mL/min and 9 (12.7%) progressed within 6-months from the end of previous neoadjuvant or adjuvant chemotherapy.

At the cut-off data of October 7, 2021, the median follow-up was 9.0 months and 13 patients are still on treatment. The median OS was 10.0 months (95% CI, 5.7-14.3), and 40.8% of patients were alive at 1-year with an estimated 1-year overall survival of 44.9%.


While PD-L1 expression of 5% or greater was required for inclusion, the authors further stratified patients according to PD-L1 expression, using a cut-off of 10%. Those with higher CPS levels (10% or greater) had longer median overall survival (13.0 vs 7.0 months, p=0.09) though comparable progression free survival (2.0 vs 2.0 months, p=0.46).


In terms of response rate, 1 patient at a complete response while 15 had partial responses. Thus, the objective response rate was 22.5%. Any grade adverse events were seen in 94.4% of patients while high-grade events were seen in 42.3%. Two grade 5 events were reported. The most common events were fever, pruritus, infusion reaction, fatigue, diarrhea, and skin rash.

Finally, in a post hoc analysis restricted to patients who received at least one month of therapy (3 infusions) (n-56), the median overall survival was 16.0 months, and the estimated 1-year overall survival was 53.9%.

Thus, the authors conclude that avelumab is active and safe as first-line therapy in patients with advanced urothelial carcinoma who have PD-L1 positive tumors who are ineligible for cisplatin.

Presented by: Roberto Iacovelli, PhD, MD, Oncology Unit, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Catholic University of Rome