Abstract 1764P
Background
Since the introduction of immune checkpoint inhibitors (ICI) for systemic treatment of metastatic urothelial carcinoma of the bladder (UCB) in 2017, the clinical value of programmed cell death 1 ligand 1 (PD-L1) as biomarker remains controversial. In 2018 European Medicines Agency (EMA) restricted approval of first-line pembrolizumab and atezolizumab in Cisplatin-ineligible patients to PD-L1 positive tumors, defined as either combined positive score (CPS) >/=10 or immune cell (IC) score 2/3. We aimed to address the clinical significance of PD-L1 positivity in patients with advanced UCB.
Methods
Patients with advanced UCB were prospectively enrolled, following radical cystectomy (RC) from January 2018 to December 2020 at our tertiary referral center. Clinical outcome defined as progression free survival (PFS) and overall survival (OS) on systemic treatment was analyzed using the χ2-test, Mann-Whitney-U-test, Kaplan-Meier method and log-rank test.
Results
PD-L1-status was analyzed as CPS and IC-score in 141 patients (43.5%) with high-risk (pT3–pT4 and/or N+) or metastatic UCB. While median PFS was 17.5 months (95%CI 11.0-24.1) for PD-L1+ patients who received ICI in 1-L, PD-L1- or PD-L1+ patients who received chemotherapy in 1-L had PFS of 3.8 (IQR 2.3-5.2) and 3.4 months (95%CI 2.9-3.9), respectively.Regardless of treatment, mean OS for PD-L1+ patients was 23.7 months (95%CI 14.9-32.5) vs. 18.2 (95%CI 5.7-30.7) for PD-L1- patients (p=0.592). Median OS with 1-L ICI was 27.2 months (95%CI 12.7-41.7) vs. 17.2 months (95%CI 10.9-23.5) with 1-L chemotherapy (p=0.311).
Conclusions
We could show that PFS largely depended on the kind of treatment given to patients, but observed no difference in OS regardless of treatment or PD-L1 status. However, the fact that PD-L1 negative patients responded to anti-PD-L1 therapy, underlines the need for reliable predictive biomarkers for agents targeting this pathway.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.