Clinical outcomes of avelumab and pembrolizumab in advanced urothelial cancer: an observational multicenter retro-prospective study on patients undergoing treatment in clinical practice (AVePEm study).

Introduction and objectives: Patients (pts) with metastatic urothelial carcinoma (mUC) gain substantial benefit from immunotherapy exposure. If they do not experience disease progression after 4-6 cycles of first-line platinum-based chemotherapy (PBC), they may benefit from immunotherapy as maintenance treatment with Avelumab; otherwise, Pembrolizumab is an approved second-line therapy after disease progression on first-line chemotherapy. However, no clinical trial data currently demonstrate which treatment strategy offers superior survival outcomes. Patients and methods: This is a multicenter, observational, retro-prospective study involving pts with mUC who did not progress after 4-6 cycles of PBC: GroupA received Avelumab and GroupB Pembrolizumab. The primary endpoints were overall survival (OS) and progression-free survival (PFS), with neutrophil-to-lymphocyte ratio (NLR) ≥3 at the baseline of PBC and at the start of immunotherapy in predicting outcome, adverse events (AEs), subsequent therapies after the immunotherapy strategy, and costs associated with these treatments as secondary endpoints. Results: From August 2019 to October 2024, we identified 30 pts. Of those, 53% were in GroupA and 47% in GroupB. The mOS in GroupA was 27 mo and in GroupB 26 mo and the mPFS of immunotherapy was 7.5 mo and 5.5 mo. At the time of data analysis, 33% (n=10) of pts were alive and 27% (n=8) on treatment, with 38% (n=3) still receiving Avelumab, and 50% (n=4) and 12% (n=1) on subsequent therapies after Avelumab and Pembrolizumab, respectively. Approximately 55% of patients in both groups had a baseline neutrophil-to-lymphocyte ratio (NLR) ≥3 at the baseline of PBC. No statistically significant association was found between NLR, whether considered as a continuous or dichotomous variable, and overall survival or progression free survival. Both treatments were well tolerated, with Grade 3 AEs in 1 pt on Avelumab and 3 on Pembrolizumab, and no Grade 4 AEs reported. Conclusions: The two immunotherapy strategies showed no significant differences in OS and PFS. Of note, more pts were on Avelumab treatment at the data cut-off. AEs were similar in the two groups. Further investigation and follow-up are warranted to gain definitive conclusions on optimal mUC management in the era of immunotherapy and immunoconjugates.