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.
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 UCpatients who received SST and no SST after progressing to ICIs. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of UCpatients 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 UCpatients 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 UCpatients who received no prior chemotherapy.
Authors: Marco Stellato; Daniele Santini; Maria Concetta Cursano; Simone Foderaro; Giuseppe Tonini; Giuseppe Procopio Journal: J Bone Oncol Date: 2021-11-28 Impact factor: 4.072
Authors: Ali Raza Khaki; Ang Li; Leonidas N Diamantopoulos; Natalie J Miller; Lucia Carril-Ajuria; Daniel Castellano; Ivan De Kouchkovsky; Vadim Koshkin; Joseph Park; Ajjai Alva; Mehmet A Bilen; Tyler Stewart; Victor Santos; Neeraj Agarwal; Jayanshu Jain; Yousef Zakharia; Rafael Morales-Barrera; Michael Devitt; Ariel Nelson; Christopher J Hoimes; Evan Shreck; Benjamin A Gartrell; Alex Sankin; Abhishek Tripathi; Roubini Zakopoulou; Aristotelis Bamias; Alejo Rodriguez-Vida; Alexandra Drakaki; Sandy Liu; Vivek Kumar; Mark P Lythgoe; David J Pinato; Jure Murgic; Ana Fröbe; Monika Joshi; Pedro Isaacsson Velho; Noah Hahn; Lucia Alonso Buznego; Ignacio Duran; Marcus Moses; Pedro Barata; Matthew D Galsky; Guru Sonpavde; Evan Y Yu; Veena Shankaran; Gary H Lyman; Petros Grivas Journal: Eur Urol Oncol Date: 2021-01-07
Authors: Nick van Dijk; Alberto Gil-Jimenez; Karina Silina; Maurits L van Montfoort; Sarah Einerhand; Lars Jonkman; Charlotte S Voskuilen; Dennis Peters; Joyce Sanders; Yoni Lubeck; Annegien Broeks; Erik Hooijberg; Daniel J Vis; Maries van den Broek; Lodewyk F A Wessels; Bas W G van Rhijn; Michiel S van der Heijden Journal: Front Immunol Date: 2021-12-20 Impact factor: 7.561
Authors: Christopher J D Wallis; Giacomo Novara; Laura Marandino; Axel Bex; Ashish M Kamat; R Jeffrey Karnes; Todd M Morgan; Nicolas Mottet; Silke Gillessen; Alberto Bossi; Morgan Roupret; Thomas Powles; Andrea Necchi; James W F Catto; Zachary Klaassen Journal: Eur Urol Date: 2020-05-03 Impact factor: 20.096