Immunotherapy Avelumab Shows Continued Survival Benefit in mUC


Results from the ARIES trial continue to show the benefit of avelumab monotherapy as a first-line drug for patients with metastatic urothelial cancer with PD-L1 expression.

The use of the immunotherapy avelumab (Bavencio) alone in the first line setting for patients with metastatic urothelial cancer (mUC) continues to show improved efficacy and safety in this setting, according to results from the multicenter, single-arm, phase II ARIES study (NCT03891238).1  

Data showed that there was continued overall survival (OS) in the 71 patients of the 198 patients with mUC enrolled and then screened for PD-L1 expression of 5% or greater. Moreover, these patients had to be ineligible for cisplatin chemotherapy and the majority of patients were ineligible for cisplatin due to a low rate of creatinine in 70.4% of patients. The median OS in this group was 10 months (95% CI, 5.5-14.5 months) and 43% of patients were alive at 1 year.

Looking at the total of 67 patients with PD-L1 expression 56 patients were classified as having high expression and among this group the median OS was 11 months (95% CI, 0.1-22.9 months). However, there was a median OS of 7 months (95% CI, 2.8-11.2 months) for patients with a low PD-L1 expression (P = 0.13) and the estimated rate of patients alive at 1 year was 48.1% in the high expression group and 27.3% in the low expression group (P = 0.32). The median progression-free survival (PFS)among both groups was 2 months (P = 0.34).

Median PFS in the overall group was 2 months (95% CI, 1.7-2.3 months) and a reduction in the targeted tumor lesions were achieved in 30 patients. The overall response rate (ORR) in this population was 24% with 6 patients who had a complete response (CR), 11 had a partial response (PR), 14 patients had stable disease (SD), and 28 patients had progressive disease with 12 patients not assessable. In the 17 patients with either a CR or PR 13 of these patients had a duration of response (DOR) of 1 year or more and 5 patients had a 2 year or more DOR.

In the patients with a high PD-L1 expression 15 had either a CR or PR, 12 patients had SD, and 21 had PD. In the patients with a low PD-L1 expression 1 patient had a PR, 1 had SD, and 5 patients had progressive disease, however, the researchers did not find these differences significant (P = 0.39).

“ARIES highlighted the essential role of clinical selection for patients eligible for immunotherapy as a cornerstone to the appropriate management of this population. Poor clinical conditions, the presence of liver metastases and non-bladder primary tumors generally characterize this group and negatively affect its outcomes,” the researchers wrote in the discussion of their results. “Even though the ECOG performance status of 2 and [patient] age were not found to influence the outcomes achieved with pembrolizumab in the KEYNOTE-052 study, we showed in a selection of patients able to receive at least 1 month of therapy with avelumab might maximize its efficacy, supporting the need for clinical and molecular predictive factors.”

The median age of this patient group was 75-years-old (range, 38-88 years) with an ECOG performance score of 1 or 2 in 77.5% of cases with most patients having a score of 1 (46.5%). Bladder cancer was the primary tumor in 73.2% of patients compared with, 43.7% and 25.3% who had lung and liver metastases, respectively, and 15.5% of patients had lymph nodes as their only site of metastasis.

Of the 38 patients with visceral metastases, they had a median OS of 7 months (95% CI, 2.8-11) compared to 11 months for those without. Of the 22 patients with an ECOG performance score of 2 their median OS was 10 months (95% CI, 0.1-24) compared to a median of 10 months (95% CI, 5.4-14.6) in those with a score of 1 or 0.

Safety remained tolerable for this patient group with adverse events (AEs) occurring in 5% or more of the patients with treatment-related AEs of any grade occurring in 35 (49.3%) of patients with grade 3 or 4 events happening in 6 (8.5%) of patients. The most common high-grade TRAE was infusion reaction occurring in 3 (4.2%) patients while the most common TRAEs in any grade were fever (29.6%), fatigue (28.2%), constipation (22.5%), anemia (21.1%), and diarrhea (19.7%). No deaths due to AEs were reported, but dose interruptions were required in 7 (9.9%) patients, and 3 (4.2%) had to discontinue treatment due to AEs.

“The ARIES trial has added evidence supporting the activity of immunotherapy alone or as the basis for upcoming combination strategies for the treatment of platinum-ineligible patients with [mUC],” the researchers concluded.


Iacovelli R, Ciccarese C, Brunelli M, et al. First-line avelumab for patients with PD-L1-positive metastatic or locally advanced urothelial cancer who are unfit for cisplatin. Ann Oncol. 2022 Nov;33(11):1179-1185. doi: 10.1016/j.annonc.2022.07.011

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