Real-world comparison of avelumab maintenance versus pembrolizumab at progression after first-line platinum-based chemotherapy in metastatic urothelial cancer

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BACKGROUND: For patients with metastatic urothelial cancer of the bladder (mUCB), the standard of care after first-line (1L) platinum-based chemotherapy has shifted from immune checkpoint inhibitor (ICI) treatment upon progression to maintenance ICI, without a direct comparison between both treatment strategies. We aimed to estimate the effect of the introduction of maintenance avelumab on overall survival (OS) compared with pembrolizumab at disease progression. MATERIALS AND METHODS: This nationwide cohort study included patients with synchronous mUCB between November 2017 and December 2023 without disease progression after four or more cycles of 1L platinum-based chemotherapy from the Netherlands Cancer Registry. Patients were grouped into the pembrolizumab era or avelumab era representing the prevailing standards of care based on the date of completing chemotherapy. Kaplan-Meier methods and multivariable flexible parametric survival models were used to compare OS, summarized as restricted mean survival time (RMST). RESULTS: We identified 308 mUCB patients, 153 in the pembrolizumab era and 155 in the avelumab era. Baseline characteristics were mostly comparable between the two groups. ICI use was 56.2% in the pembrolizumab era and 72.3% in the avelumab era ( P = 0.05). Adjusted RMST difference (avelumab era - pembrolizumab era) up to 24 months was 0.7 months (95% confidence interval -1.1 to 2.3). CONCLUSION: No improved survival was observed following the change in standard of care from pembrolizumab at progression to avelumab maintenance, though more patients received ICI. These findings suggest that a treatment-free interval after chemotherapy, followed by ICI at progression, may be as effective as immediate maintenance ICI therapy, while minimizing toxicity, treatment burden, and healthcare resource use.

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