TY - JOUR
T1 - Association of prior local therapy and outcomes with programmed-death ligand-1 inhibitors in advanced urothelial cancer
AU - Makrakis, Dimitrios
AU - Talukder, Rafee
AU - Diamantopoulos, Leonidas N.
AU - Carril-Ajuria, Lucia
AU - Castellano, Daniel
AU - De Kouchkovsky, Ivan
AU - Koshkin, Vadim S.
AU - Park, Joseph J.
AU - Alva, Ajjai
AU - Bilen, Mehmet A.
AU - Stewart, Tyler F.
AU - McKay, Rana R.
AU - Santos, Victor S.
AU - Agarwal, Neeraj
AU - Jain, Jayanshu
AU - Zakharia, Yousef
AU - Morales-Barrera, Rafael
AU - Devitt, Michael E.
AU - Grant, Michael
AU - Lythgoe, Mark P.
AU - Pinato, David J.
AU - Nelson, Ariel
AU - Hoimes, Christopher J.
AU - Shreck, Evan
AU - Gartrell, Benjamin A.
AU - Sankin, Alex
AU - Tripathi, Abhishek
AU - Zakopoulou, Roubini
AU - Bamias, Aristotelis
AU - Murgic, Jure
AU - Fröbe, Ana
AU - Rodriguez-Vida, Alejo
AU - Drakaki, Alexandra
AU - Liu, Sandy
AU - Kumar, Vivek
AU - Di Lorenzo, Giuseppe
AU - Joshi, Monika
AU - Isaacsson-Velho, Pedro
AU - Buznego, Lucia Alonso
AU - Duran, Ignacio
AU - Moses, Marcus
AU - Barata, Pedro
AU - Sonpavde, Guru
AU - Yu, Evan Y.
AU - Wright, Jonathan L.
AU - Grivas, Petros
AU - Khaki, Ali Raza
N1 - Publisher Copyright:
© 2022 BJU International.
PY - 2022/11
Y1 - 2022/11
N2 - Objectives: To compare clinical outcomes with programmed-death ligand-1 immune checkpoint inhibitors (ICIs) in patients with advanced urothelial carcinoma (aUC) who have vs have not undergone radical surgery (RS) or radiation therapy (RT) prior to developing metastatic disease. Patients and Methods: We performed a retrospective cohort study collecting clinicopathological, treatment and outcomes data for patients with aUC receiving ICIs across 25 institutions. We compared outcomes (observed response rate [ORR], progression-free survival [PFS], overall survival [OS]) between patients with vs without prior RS, and by type of prior locoregional treatment (RS vs RT vs no locoregional treatment). Patients with de novo advanced disease were excluded. Analysis was stratified by treatment line (first-line and second-line or greater [second-plus line]). Logistic regression was used to compare ORR, while Kaplan–Meier analysis and Cox regression were used for PFS and OS. Multivariable models were adjusted for known prognostic factors. Results: We included 562 patients (first-line: 342 and second-plus line: 220). There was no difference in outcomes based on prior locoregional treatment among those treated with first-line ICIs. In the second-plus-line setting, prior RS was associated with higher ORR (adjusted odds ratio 2.61, 95% confidence interval [CI]1.19–5.74]), longer OS (adjusted hazard ratio [aHR] 0.61, 95% CI 0.42–0.88) and PFS (aHR 0.63, 95% CI 0.45–0.89) vs no prior RS. This association remained significant when type of prior locoregional treatment (RS and RT) was modelled separately. Conclusion: Prior RS before developing advanced disease was associated with better outcomes in patients with aUC treated with ICIs in the second-plus-line but not in the first-line setting. While further validation is needed, our findings could have implications for prognostic estimates in clinical discussions and benchmarking for clinical trials. Limitations include the study’s retrospective nature, lack of randomization, and possible selection and confounding biases.
AB - Objectives: To compare clinical outcomes with programmed-death ligand-1 immune checkpoint inhibitors (ICIs) in patients with advanced urothelial carcinoma (aUC) who have vs have not undergone radical surgery (RS) or radiation therapy (RT) prior to developing metastatic disease. Patients and Methods: We performed a retrospective cohort study collecting clinicopathological, treatment and outcomes data for patients with aUC receiving ICIs across 25 institutions. We compared outcomes (observed response rate [ORR], progression-free survival [PFS], overall survival [OS]) between patients with vs without prior RS, and by type of prior locoregional treatment (RS vs RT vs no locoregional treatment). Patients with de novo advanced disease were excluded. Analysis was stratified by treatment line (first-line and second-line or greater [second-plus line]). Logistic regression was used to compare ORR, while Kaplan–Meier analysis and Cox regression were used for PFS and OS. Multivariable models were adjusted for known prognostic factors. Results: We included 562 patients (first-line: 342 and second-plus line: 220). There was no difference in outcomes based on prior locoregional treatment among those treated with first-line ICIs. In the second-plus-line setting, prior RS was associated with higher ORR (adjusted odds ratio 2.61, 95% confidence interval [CI]1.19–5.74]), longer OS (adjusted hazard ratio [aHR] 0.61, 95% CI 0.42–0.88) and PFS (aHR 0.63, 95% CI 0.45–0.89) vs no prior RS. This association remained significant when type of prior locoregional treatment (RS and RT) was modelled separately. Conclusion: Prior RS before developing advanced disease was associated with better outcomes in patients with aUC treated with ICIs in the second-plus-line but not in the first-line setting. While further validation is needed, our findings could have implications for prognostic estimates in clinical discussions and benchmarking for clinical trials. Limitations include the study’s retrospective nature, lack of randomization, and possible selection and confounding biases.
KW - #BladderCancer
KW - #blcsm
KW - #uroonc
KW - #utuc
KW - bladder cancer
KW - immune checkpoint inhibitors
KW - immunotherapy
KW - outcomes
KW - urinary tract neoplasms
KW - urothelial carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85117760063&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85117760063&partnerID=8YFLogxK
U2 - 10.1111/bju.15603
DO - 10.1111/bju.15603
M3 - Article
C2 - 34597472
AN - SCOPUS:85117760063
SN - 1464-4096
VL - 130
SP - 592
EP - 603
JO - BJU International
JF - BJU International
IS - 5
ER -