Clinical outcome after progressing to frontline and second-line Anti-PD-1/PD-L1 in advanced urothelial cancer.

Autor: Gómez de Liaño Lista A; St. Bartholomew Hospital, London, UK; Complejo Hospitalario Universitario Insular-Materno Infantil, Las Palmas, Spain. Electronic address: Alfonso.gomezdeliano@nhs.net., van Dijk N; Netherlands Cancer Institute, Amsterdam, The Netherlands., de Velasco Oria de Rueda G; Hospital 12 de Octubre, Madrid, Spain., Necchi A; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy., Lavaud P; Gustave Roussy, Paris, France., Morales-Barrera R; Hospital Vall d´Hebron, Barcelona, Spain., Alonso Gordoa T; Hospital Ramón y Cajal, Madrid, Spain., Maroto P; Hospital de la Santa Creu I Sant Pau, Barcelona, Spain., Ravaud A; Centre Hospitalier Universitaire, Bordeaux, France., Durán I; Hospital Marqués de Valdecilla-IDIVAL, Santander, Spain., Szabados B; St. Bartholomew Hospital, London, UK., Castellano D; Hospital 12 de Octubre, Madrid, Spain., Giannatempo P; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy., Loriot Y; Gustave Roussy, Paris, France., Carles J; Hospital Vall d´Hebron, Barcelona, Spain., Anguera Palacios G; Hospital de la Santa Creu I Sant Pau, Barcelona, Spain., Lefort F; Centre Hospitalier Universitaire, Bordeaux, France., Raggi D; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy., Gross Goupil M; Centre Hospitalier Universitaire, Bordeaux, France., Powles T; St. Bartholomew Hospital, London, UK., Van der Heijden MS; Netherlands Cancer Institute, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: European urology [Eur Urol] 2020 Feb; Vol. 77 (2), pp. 269-276. Date of Electronic Publication: 2019 Nov 05.
DOI: 10.1016/j.eururo.2019.10.004
Abstrakt: Background: Immune checkpoint inhibitors (ICIs) are approved for first-line (cisplatin unfit, PD-L1+) and platinum-refractory urothelial carcinoma (UC). Still, most patients experience progressive disease (PD) as the best response. Although higher response rates to subsequent systemic treatment (SST) have been described, post-PD outcome data are scarce.
Objective: To examine the outcome of UC patients who received SST and no SST after progressing to ICIs.
Design, Setting, and Participants: A retrospective analysis of UC patients progressing to frontline or later-line anti-PD-1/PD-L1 therapy in 10 European institutions was conducted between March 2013 and September 2017.
Intervention: Post-PD management as per standard practice.
Outcome Measurements and Statistical Analysis: Overall survival (OS) was analyzed with a Kaplan-Meier model. Cox regression was used for multivariate analysis (MV). Impact of SST on OS was examined with a time-varying covariate model.
Results and Limitations: A total of 270 UC patients with PD to ICIs (69 frontline, 201 later line) were analyzed. Of the patients, 57% of frontline-ICI-PD and 34% of later-line-ICI-PD patients received SST, and SST had an impact on OS in MV (frontline: hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.10-0.51, p <  0.001; later line: HR 0.22, 95% CI 0.13-0.36, p <  0.001). In the frontline-ICI-PD group, median OS with and without SST was 6.8 mo (95% CI 5.0-8.6) and 1.9 mo (95% CI 0.9-3.0), respectively. High disease burden (three or more metastatic sites: HR 2.49, p =  0.03; simultaneous liver/bone metastases: HR 3.93, p =  0.03) predicted worse survival. In later-line-ICI-PD group, response to ICIs (HR 0.37, p =  0.03), longer exposure to ICIs (HR 0.89, p =  0.002), and bone metastasis (HR 2.42, p <  0.001) predicted survival. The retrospective nature of this study and a lack of certain parameters limit the interpretation of our analysis.
Conclusions: Patients progressing to frontline ICIs are at risk of early death, excluding them from experiencing potential benefit from chemotherapy PATIENT SUMMARY: Our analysis suggests that outcomes after failing immunotherapy are poor, particularly in UC patients who received no prior chemotherapy.
(Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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