Association Between Sites of Metastasis and Outcomes With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

Dimitrios Makrakis; Rafee Talukder; Genevieve Ihsiu Lin; Leonidas N. Diamantopoulos; Scott Dawsey; Shilpa Gupta; Lucia Carril-Ajuria; Daniel Castellano; Ivan de Kouchkovsky; Vadim S. Koshkin; Joseph J. Park; Ajjai Alva; Mehmet A. Bilen; Tyler F. Stewart; Rana R. McKay; Nishita Tripathi; Neeraj Agarwal; Naomi Vather-Wu; Yousef Zakharia; Rafael Morales-Barrera; Michael E. Devitt; Alessio Cortellini; Claudia Angela Maria Fulgenzi; David J. Pinato; Ariel Nelson; Christopher J. Hoimes; Kavita Gupta; Benjamin A. Gartrell; Alex Sankin; Abhishek Tripathi; Roubini Zakopoulou; Aristotelis Bamias; Jure Murgic; Ana Fröbe; Alejo Rodriguez-Vida; Alexandra Drakaki; Sandy Liu; Eric Lu; Vivek Kumar; Giuseppe Di Lorenzo; Monika Joshi; Pedro Isaacsson-Velho; Lucia Alonso Buznego; Ignacio Duran; Marcus Moses; Albert Jang; Pedro Barata; Guru Sonpavde; Evan Y. Yu; Robert Bruce Montgomery; Petros Grivas; Ali Raza Khaki

doi:10.1016/j.clgc.2022.06.001

Association Between Sites of Metastasis and Outcomes With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

Dimitrios Makrakis, Rafee Talukder, Genevieve Ihsiu Lin, Leonidas N. Diamantopoulos, Scott Dawsey, Shilpa Gupta, Lucia Carril-Ajuria, Daniel Castellano, Ivan de Kouchkovsky, Vadim S. Koshkin, Joseph J. Park, Ajjai Alva, Mehmet A. Bilen, Tyler F. Stewart, Rana R. McKay, Nishita Tripathi, Neeraj Agarwal, Naomi Vather-Wu, Yousef Zakharia, Rafael Morales-BarreraMichael E. Devitt, Alessio Cortellini, Claudia Angela Maria Fulgenzi, David J. Pinato, Ariel Nelson, Christopher J. Hoimes, Kavita Gupta, Benjamin A. Gartrell, Alex Sankin, Abhishek Tripathi, Roubini Zakopoulou, Aristotelis Bamias, Jure Murgic, Ana Fröbe, Alejo Rodriguez-Vida, Alexandra Drakaki, Sandy Liu, Eric Lu, Vivek Kumar, Giuseppe Di Lorenzo, Monika Joshi, Pedro Isaacsson-Velho, Lucia Alonso Buznego, Ignacio Duran, Marcus Moses, Albert Jang, Pedro Barata, Guru Sonpavde, Evan Y. Yu, Robert Bruce Montgomery, Petros Grivas, Ali Raza Khaki

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Sites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI. Methods: We identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd⁺ line. Results: We identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd⁺ line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd⁺ line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant. Conclusion: Bone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses.

Original language	English (US)
Pages (from-to)	e440-e452
Journal	Clinical Genitourinary Cancer
Volume	20
Issue number	5
DOIs	https://doi.org/10.1016/j.clgc.2022.06.001
State	Published - Oct 2022

Keywords

Advanced urothelial carcinoma
Bladder cancer
Immune checkpoint inhibitors
Metastatic cancer
Outcomes

ASJC Scopus subject areas

Oncology
Urology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.clgc.2022.06.001

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Makrakis, D., Talukder, R., Lin, G. I., Diamantopoulos, L. N., Dawsey, S., Gupta, S., Carril-Ajuria, L., Castellano, D., de Kouchkovsky, I., Koshkin, V. S., Park, J. J., Alva, A., Bilen, M. A., Stewart, T. F., McKay, R. R., Tripathi, N., Agarwal, N., Vather-Wu, N., Zakharia, Y., ... Khaki, A. R. (2022). Association Between Sites of Metastasis and Outcomes With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma. Clinical Genitourinary Cancer, 20(5), e440-e452. https://doi.org/10.1016/j.clgc.2022.06.001

Makrakis, D, Talukder, R, Lin, GI, Diamantopoulos, LN, Dawsey, S, Gupta, S, Carril-Ajuria, L, Castellano, D, de Kouchkovsky, I, Koshkin, VS, Park, JJ, Alva, A, Bilen, MA, Stewart, TF, McKay, RR, Tripathi, N, Agarwal, N, Vather-Wu, N, Zakharia, Y, Morales-Barrera, R, Devitt, ME, Cortellini, A, Fulgenzi, CAM, Pinato, DJ, Nelson, A, Hoimes, CJ, Gupta, K, Gartrell, BA , Sankin, A, Tripathi, A, Zakopoulou, R, Bamias, A, Murgic, J, Fröbe, A, Rodriguez-Vida, A, Drakaki, A, Liu, S, Lu, E, Kumar, V, Lorenzo, GD, Joshi, M, Isaacsson-Velho, P, Buznego, LA, Duran, I, Moses, M, Jang, A, Barata, P, Sonpavde, G, Yu, EY, Montgomery, RB, Grivas, P & Khaki, AR 2022, 'Association Between Sites of Metastasis and Outcomes With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma', Clinical Genitourinary Cancer, vol. 20, no. 5, pp. e440-e452. https://doi.org/10.1016/j.clgc.2022.06.001

@article{d569c961a5c04b8ba758e70f387a241d,

title = "Association Between Sites of Metastasis and Outcomes With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma",

abstract = "Background: Sites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI. Methods: We identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd+ line. Results: We identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd+ line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd+ line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant. Conclusion: Bone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses.",

keywords = "Advanced urothelial carcinoma, Bladder cancer, Immune checkpoint inhibitors, Metastatic cancer, Outcomes",

author = "Dimitrios Makrakis and Rafee Talukder and Lin, {Genevieve Ihsiu} and Diamantopoulos, {Leonidas N.} and Scott Dawsey and Shilpa Gupta and Lucia Carril-Ajuria and Daniel Castellano and {de Kouchkovsky}, Ivan and Koshkin, {Vadim S.} and Park, {Joseph J.} and Ajjai Alva and Bilen, {Mehmet A.} and Stewart, {Tyler F.} and McKay, {Rana R.} and Nishita Tripathi and Neeraj Agarwal and Naomi Vather-Wu and Yousef Zakharia and Rafael Morales-Barrera and Devitt, {Michael E.} and Alessio Cortellini and Fulgenzi, {Claudia Angela Maria} and Pinato, {David J.} and Ariel Nelson and Hoimes, {Christopher J.} and Kavita Gupta and Gartrell, {Benjamin A.} and Alex Sankin and Abhishek Tripathi and Roubini Zakopoulou and Aristotelis Bamias and Jure Murgic and Ana Fr{\"o}be and Alejo Rodriguez-Vida and Alexandra Drakaki and Sandy Liu and Eric Lu and Vivek Kumar and Lorenzo, {Giuseppe Di} and Monika Joshi and Pedro Isaacsson-Velho and Buznego, {Lucia Alonso} and Ignacio Duran and Marcus Moses and Albert Jang and Pedro Barata and Guru Sonpavde and Yu, {Evan Y.} and Montgomery, {Robert Bruce} and Petros Grivas and Khaki, {Ali Raza}",

note = "Funding Information: D Makrakis and LN Diamantopoulos acknowledge the support of Kure It Cancer Research. P Grivas, EY Yu, RB Montgomery acknowledge the support of the Seattle Translational Tumor Research Program at Fred Hutchinson Cancer Center. DJ. Pinato acknowledges the infrastructure support provided by Imperial Experimental Cancer Medicine Centre, Cancer Research UK Imperial Centre, the Imperial College Healthcare NHS Trust Tissue Bank and the Imperial College BRC. AR Khaki and R Talukder were supported by the National Cancer Institute under training grant T32CA009515 . Research Electronic Data Capture at the Institute of Translational Health Sciences is supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award UL1 TR002319 . David J. Pinato is supported by grant funding from the Wellcome Trust Strategic Fund ( PS3416 ) and acknowledges grant support from the Cancer Treatment and Research Trust (CTRT) and infrastructural support by the Cancer Research UK Imperial Centre and the NIHR Imperial Biomedical Research Centre. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2022",

month = oct,

doi = "10.1016/j.clgc.2022.06.001",

language = "English (US)",

volume = "20",

pages = "e440--e452",

journal = "Clinical Genitourinary Cancer",

issn = "1558-7673",

publisher = "Elsevier",

number = "5",

}

TY - JOUR

T1 - Association Between Sites of Metastasis and Outcomes With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

AU - Makrakis, Dimitrios

AU - Talukder, Rafee

AU - Lin, Genevieve Ihsiu

AU - Diamantopoulos, Leonidas N.

AU - Dawsey, Scott

AU - Gupta, Shilpa

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 - Tripathi, Nishita

AU - Agarwal, Neeraj

AU - Vather-Wu, Naomi

AU - Zakharia, Yousef

AU - Morales-Barrera, Rafael

AU - Devitt, Michael E.

AU - Cortellini, Alessio

AU - Fulgenzi, Claudia Angela Maria

AU - Pinato, David J.

AU - Nelson, Ariel

AU - Hoimes, Christopher J.

AU - Gupta, Kavita

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 - Lu, Eric

AU - Kumar, Vivek

AU - Lorenzo, Giuseppe Di

AU - Joshi, Monika

AU - Isaacsson-Velho, Pedro

AU - Buznego, Lucia Alonso

AU - Duran, Ignacio

AU - Moses, Marcus

AU - Jang, Albert

AU - Barata, Pedro

AU - Sonpavde, Guru

AU - Yu, Evan Y.

AU - Montgomery, Robert Bruce

AU - Grivas, Petros

AU - Khaki, Ali Raza

N1 - Funding Information: D Makrakis and LN Diamantopoulos acknowledge the support of Kure It Cancer Research. P Grivas, EY Yu, RB Montgomery acknowledge the support of the Seattle Translational Tumor Research Program at Fred Hutchinson Cancer Center. DJ. Pinato acknowledges the infrastructure support provided by Imperial Experimental Cancer Medicine Centre, Cancer Research UK Imperial Centre, the Imperial College Healthcare NHS Trust Tissue Bank and the Imperial College BRC. AR Khaki and R Talukder were supported by the National Cancer Institute under training grant T32CA009515 . Research Electronic Data Capture at the Institute of Translational Health Sciences is supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award UL1 TR002319 . David J. Pinato is supported by grant funding from the Wellcome Trust Strategic Fund ( PS3416 ) and acknowledges grant support from the Cancer Treatment and Research Trust (CTRT) and infrastructural support by the Cancer Research UK Imperial Centre and the NIHR Imperial Biomedical Research Centre. Publisher Copyright: © 2022 Elsevier Inc.

PY - 2022/10

Y1 - 2022/10

N2 - Background: Sites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI. Methods: We identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd+ line. Results: We identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd+ line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd+ line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant. Conclusion: Bone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses.

AB - Background: Sites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI. Methods: We identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd+ line. Results: We identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd+ line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd+ line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant. Conclusion: Bone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses.

KW - Advanced urothelial carcinoma

KW - Bladder cancer

KW - Immune checkpoint inhibitors

KW - Metastatic cancer

KW - Outcomes

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U2 - 10.1016/j.clgc.2022.06.001

DO - 10.1016/j.clgc.2022.06.001

M3 - Article

C2 - 35778337

AN - SCOPUS:85133310824

SN - 1558-7673

VL - 20

SP - e440-e452

JO - Clinical Genitourinary Cancer

JF - Clinical Genitourinary Cancer

IS - 5

ER -

Association Between Sites of Metastasis and Outcomes With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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