Artikel
Clinical activity of immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma and the role of subsequent therapies, a single-center evaluation
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Autoren
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Aykhan Isgandarov
- Universitätsklinikum Essen, Essen, Germany
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Christopher Darr
- Universitätsklinikum Essen, Essen, Germany
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Ullrich Krafft
- Universitätsklinikum Essen, Essen, Germany
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Lukas Puellen
- Universitätsklinikum Essen, Essen, Germany
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Boris Alexander Hadaschik
- Universitätsklinikum Essen, Essen, Germany
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Viktor Gruenwald
- Universitätsklinikum Essen, Essen, Germany; Westdeutsches Tumorzentrum Essen, Essen, Germany
| Veröffentlicht: | 28. März 2023 |
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Gliederung
Text
Background: Immune checkpoint inhibitor (ICI) therapy is a standard of care for metastatic urothelial carcinoma (mUC). We aimed to evaluate the clinical efficacy of palliative chemotherapy (CT) after failure of ICI treatment.
Methods: This retrospective analysis evaluated clinical efficacy of ICI in 1L and 2L treatment and outcome of Patients, who received in 2L and 3 L a CT after ICI. The patients who received palliative ICI system therapy in one of the three lines at the West German Tumor Center Essen (WTZE) between June 2016 and July 2021 were included. mUC with or without variant differentiation were allowed. Primary endpoint was objective response rate (ORR) according to RECIST 1.1. Secondary endpoints were progression-free survival (PFS), defined as the time from initiation of therapy to progression or death from any cause and toxicities according to CTCAEv5.0. Patients who died before a second tumor scan were counted as progressive disease (PD). KM plots, log-rank analyses and descriptive statistics were performed.
Results: 53 eligible patients (79.2% male) were analyzed. ECOG 0–1 was 92.5% (n=49). mUC without variant histology was reported in 75.5% (n=40). Median age at start of first line (1L) therapy was 66.8 (IQR: 56.6; 75.4). 22.6% had liver metastases and 54.7% had creatinine clearance < 60 ml/min. ICI was applied as: 1L 49.1% (n=26), 2L 39.6% (n=21) or 3L 5.7% (n=3) treatment, respectively. 1L ORR of ICI was 53.9% (PR: 46.2%, CR: 7.7%), SD was 7.7% and PD 38.5%. Median PFS of 1L ICI treatment was 2.4 months. Discontinuation of 1L ICI therapy was due to PD in 30.8% and toxicity in 23.1%, respectively. 2L ORR of ICI was 23.8% (PR: 14.3%, CR: 9.5%), SD was 19% and PD 57.1%. Median PFS of 2L was 3.4 months. Discontinuation of 2L ICI therapy was due to PD in 57.1% and toxicity in 19%, respectively. 3 of 26 patients from 1L ICI received a CT as 2L and 9 of 21 from 2L ICI received a CT as 3L. ORR of the patients who received a CT post ICI was 25% (CR: 8.3%, PR: 16.7%), SD was 16.7% and PD 58.3%. Median post ICI treatment duration and PFS were 1.4 and 3 months (95% CI 2.6–3.4), respectively. Median overall survival was 7.2 Months (95% CI 3.7–10.7).
Conclusions: Post-ICI chemotherapy showed modest clinical activity. Major limitations are number of patients and retrospective study design.
