Sequencing of PD-1/L1 inhibitors and carboplatin based chemotherapy for cisplatin ineligible metastatic urothelial carcinoma Journal Article


Authors: Wei, X. X.; Werner, L.; Teo, M. Y.; Rosenberg, J. E.; Koshkin, V. S.; Grivas, P.; Szabados, B.; Morrison, L.; Powles, T.; Carril-Ajuria, L.; Castellano, D.; Velho, P. I.; Hahn, N. M.; McKay, R. R.; Raggi, D.; Necchi, A.; Kanesvaran, R.; Alerasool, P.; Gaines, J.; Galsky, M.; Bellmunt, J.; Sonpavde, G.
Article Title: Sequencing of PD-1/L1 inhibitors and carboplatin based chemotherapy for cisplatin ineligible metastatic urothelial carcinoma
Abstract: PURPOSE: Current first line treatment options in patients with metastatic urothelial carcinoma unfit to receive cisplatin containing chemotherapy include PD-1/L1 inhibitors and carboplatin containing chemotherapy. However, the optimal sequencing of these therapies remains unclear. MATERIALS AND METHODS: We conducted a multicenter retrospective analysis. Consecutive cisplatin ineligible patients with metastatic urothelial carcinoma treated with first line carboplatin containing chemotherapy followed sequentially by second line PD-1/L1 inhibitor, or the reverse order, were included. Patient demographics, objective response, time to treatment failure for first line and second line therapy, interval between end of first line and initiation of second line treatment (Interval1L-2L) and overall survival were collected. Multivariate analysis was conducted to examine the association of sequencing on overall survival. RESULTS: In this multicenter retrospective study we identified 146 cisplatin ineligible patients with metastatic urothelial carcinoma treated with first line PD-1/L1 inhibitor therapy followed by second line carboplatin containing chemotherapy (group 1, 43) or the reverse sequence (group 2, 103). In the overall cohort median age was 72, 76% were men and 18% had liver metastasis. In both groups objective response rates were higher with carboplatin containing chemotherapy (45.6% first line, 44.2% second line) compared to PD-1/L1 inhibitors (9.3% first line, 21.3% second line). On multivariate analysis treatment sequence was not associated with overall survival (HR 1.05, p=0.85). Site of metastasis was the only factor significantly associated with overall survival (p=0.002). CONCLUSIONS: In this biomarker unselected cohort of cisplatin ineligible patients with metastatic urothelial carcinoma, PD-1/L1 inhibitor followed by carboplatin containing chemotherapy and the reverse sequence had comparable overall survival.
Keywords: carboplatin; urinary bladder neoplasms; carcinoma; transitional cell; programmed cell death 1 receptor
Journal Title: Journal of Urology
Volume: 205
Issue: 2
ISSN: 0022-5347
Publisher: Elsevier Science, Inc.  
Date Published: 2021-02-01
Start Page: 414
End Page: 419
Language: English
DOI: 10.1097/ju.0000000000001371
PUBMED: 32935617
PROVIDER: scopus
PMCID: PMC8715311
DOI/URL:
Notes: Article -- Export Date: 1 March 2021 -- Source: Scopus
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  1. Jonathan Eric Rosenberg
    513 Rosenberg
  2. Min Yuen   Teo
    105 Teo