Checkpoint Inhibition for Metastatic Urothelial Carcinoma After Chemotherapy—Real-World Clinical Impressions and Comparative Review of the Literature

Abstract

Background: The introduction of checkpoint inhibitors is a long-awaited new option for a urothelial cancer with a poor prognosis. Apart from clinical studies, the data on real world experience is scarce. Methods: Patients for monotherapy with either Atezolizumab, Nivolumab or Pembrolizumab after chemotherapy were included. Adverse events and immune related adverse events as well as survival data and imaging analyses were recorded in a prospectively designed multi-center data base. Duration of response, progression free survival (PFS), and overall survival (OS) were estimated with the Kaplan-Meier method. Results: A total of 28 patients were included. The median follow-up was 8.0 (range, 0.7-41.7) months. Median PFS was 5.8 (95% CI, 2.3-NA) months. Median OS for all patients was 10.0 (95% CI, 8.0-NA) months. The overall response rate (ORR) was 21.4% (6 out of 28 patients). Adverse events were recorded in 20 (71.4%) of patients. Higher grade adverse events (≥Grade 3) were present in 11 (39.3%) patients. No therapy related deaths occurred during the observation period. A total of 13 (46.4%) patients had adverse events that were considered to be immune related. The most commonly affected organ was the thyroid gland with 21.4% of events. Conclusion: Our real-world clinical series confirms an objective response for about every fifth patient, promising OS and a low incidence for severe adverse events (≥Grade 3).

Efficacy and Safety of Checkpoint Inhibitor Treatment in Patients with Advanced Renal or Urothelial Cell Carcinoma and Concomitant Chronic Kidney Disease: A Retrospective Cohort Study

“…For patients with UC, OS was 18.84 months in CKD patients, and was 15.47 months in patients with normal renal function. The survival of the latter group was longer than reported in previous real-world datasets and prospective trials [ 6 , 14 , 21 , 25 , 32 ]. Our finding is surprising at first sight, as CKD has often been associated with worse OS, potentially as a result of the ineligibility of these patients for adjuvant and/or standard treatments [ 33 ].…”

Effectiveness and safety profile of pembrolizumab for metastatic urothelial cancer: A retrospective single‐center analysis in Japan

“…Metastatic urothelial cancer (UC) is associated with a poor prognosis. 1 , 2 Platinum‐based chemotherapy has been the gold standard for this metastatic disease since 1985 and the introduction of methotrexate, vinblastine, adriamycin, cisplatin chemotherapy. 3 No standard second‐line treatment has been established, consequently, metastatic UC is a generally fatal disease with overall survival (OS) of 6–7 months after the failure of first‐line chemotherapy.…”

Immuntherapien in der Uroonkologie

“…Die Therapiealgorithmen des NCC und UCA befinden sich in einem stetigen Wandel mit neuen Mono-oder Kombinationstherapien [4][5][6][11][12][13] Im Vergleich der UCA-Patientenkohorte zu denen der Zulassungsstudie ist das mediane Alter ähnlich (medianes Alter 72, 74 und 77 Jahre; [11,17,18]). Die Rate an Patienten mit Lebermetastasen, ein schlechter Prognosefaktor für das Überleben im UCA waren in den Zulassungsstudien etwas hö- Die zahlreichen Mono-und Kombinationstherapien machen es aktuell und auch zukünftig immer komplexer, eine verlässliche Real-world-Erfahrung zu schaffen.…”

“…In den Real-world-Daten konnten die Ergebnisse aus den Zulassungsstudien bestätigt werden: Etwa jeder 5. Patient wies Nebenwirkungen auf, die zu einer Therapieunterbrechung führten [4][5][6][9][10][11]. Wie die verschiedenen Studien bereits gezeigt haben, war in der vorliegenden Analyse die Hyper-oder Hypothyreose die am häufigsten festgestellte Nebenwirkung, welche gut therapiert werden konnte und in den seltensten Fällen zu einer Therapieunterbrechung geführt hat (Daten nicht gezeigt).…”