First-line treatment with the PD-L1 antibody avelumab failed to meet the primary endpoint of an improvement in overall survival at 1 year for patients with cisplatin-ineligible, PD-L1–positive advanced urothelial cancer. However, the objective response and disease control rates were favorable in that subgroup of patients, according to results of the phase II ARIES trial, presented at the 2022 ASCO Genitourinary Cancers Symposium.¹ At a median follow-up of 9 months, median overall survival was 10 months. The 1-year survival rate was 40.8%.

“The ARIES trial confirmed the favorable safety profile of avelumab in advanced urothelial cancer. Although avelumab was unable to improve the 1-year overall survival rate as expected, patients able to receive at least 1 month of therapy had longer overall survival,” said lead study author

Roberto Iacovelli, MD, PhD

Roberto Iacovelli, MD, PhD, a medical oncologist at the Fondazione Policlinico Gemelli IRCCS, Rome. “Patients with advanced urothelial cancer who are unfit for cisplatin have a dismal prognosis. Clinical selection is critical to maximize the efficacy of available therapeutic options, including immunotherapy,” Dr. Iacovelli concluded.

Standard first-line treatment of advanced urothelial cancer is cisplatin-based chemotherapy. However, about 50% of these patients are ineligible for cisplatin, and some are ineligible for any platinum, which is associated with a poor prognosis. Avelumab has demonstrated improved progression-free and overall survival as maintenance therapy in patients with advanced urothelial cancer with responsive or stable disease after first-line platinum-based therapy.

Study Details

The single-arm, multisite, open-label phase II ARIES trial evaluated the efficacy and safety of avelumab in patients with cisplatin-ineligible, PD-L1–positive advanced urothelial cancer.

Enrolled patients had a histologic diagnosis of advanced urothelial cancer, an ECOG performance status of 0 to 2, and cisplatin-ineligible disease due to at least one of the following factors: ECOG performance status of 2; glomerular filtration rate < 60 mL/min; grade 2 or worse peripheral neuropathy or hearing loss; prior cisplatin neoadjuvant or adjuvant chemotherapy; and disease progression within 6 months before the end of cisplatin neoadjuvant or adjuvant chemotherapy.

A total of 198 patients underwent central assessment for PD-L1 expression of at least 5%. A total of 71 eligible patients received 10 mg/kg of intravenous avelumab every 2 weeks and were treated until disease progression, unacceptable toxicity, or study withdrawal, whichever occurred first. The primary endpoint was 1-year overall survival.

Among enrolled patients, 70.4% had creatinine clearance < 60 mL/min, 31% had an ECOG performance status of 2, 5.8% had grade 2 or worse peripheral neuropathy or hearing loss, and 12.7% had disease progression within 6 months from the end of neoadjuvant/adjuvant chemotherapy. At baseline, 56 patients had a PD-L1 combined positive score (CPS) ≥ 10, 11 had a CPS score < 10, and 4 were not evaluable.

Key Results

Median overall survival was 13 months in patients with a CPS of at least 10 vs 7 months in patients with a CPS below 10, which was numerically but not statistically significant (P = .09). The 1-year survival rates were 50.4% in the group with a CPS of at least 10 and 27.3% in the group with a CPS less than 10; the 2-year overall survival rates were 39% and 14%, respectively. In the overall study population, median progression-free survival was 2 months. According to PD-L1 status, median progression-free survival was similar in the groups with a CPS greater than and less than 10.

Confirmed objective response rate as per Response Evaluation Criteria in Solid Tumors was 22.5% (n = 16), including 1 complete response (1.4%) and 15 partial responses (21.1%). Stable disease was reported in 15 patients (21.1%), for a disease control rate of 43.6%. A post hoc analysis in patients who received at least 1 month of therapy or three treatment infusions (n = 56) found that the median overall survival was 16 months. The estimated 1-year rate of overall survival was 53.9%.

Any-grade adverse effects were reported in 67 patients (94.4%), and grade 3 to 5 adverse events occurred in 30 patients (42.3%). Fatal adverse events (none treatment-related) were reported in two patients (2.8%). 

DISCLOSURE: Dr. Iacovelli has received honoraria from Ipsen, MSD, and Pfizer; has served as a consultant or advisor to Astellas Pharma, Janssen, Merck, Novartis, Pfizer, and Sanofi; has served on a speakers bureau for Ipsen, Janssen, MSD, Pfizer, and Sanofi; has received institutional research funding from Pfizer; and has received reimbursement for travel, accommodations, and expenses from Ipsen, Janssen, and Pfizer.

REFERENCE

1. Iacovelli R, et al: 2022 ASCO Genitourinary Cancers Symposium. Abstract 439. Presented February 19, 2022.