Nationwide Real-World Outcomes of Trial Eligible and Trial Ineligible Patients With Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab

Mette Syberg Jespersen; Jesper Andreas Evers Palshof; Niels Fristrup; Niels Viggo Jensen; Jon Røikjær Henriksen; Ane Bundsbæk Bøndergaard Iversen; Sarah Grønbech Steen; Morten Andersen; Kasper Madsen; Inge Marie Svane; Anne Kirstine Møller Darras

doi:10.1016/j.clgc.2025.102450

Nationwide Real-World Outcomes of Trial Eligible and Trial Ineligible Patients With Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab

Mette Syberg Jespersen^*, Jesper Andreas Evers Palshof, Niels Fristrup, Niels Viggo Jensen, Jon Røikjær Henriksen, Ane Bundsbæk Bøndergaard Iversen, Sarah Grønbech Steen, Morten Andersen, Kasper Madsen, Inge Marie Svane, Anne Kirstine Møller Darras

^*Corresponding author for this work

3 Citations (Scopus)

Abstract

INTRODUCTION: Clinical trials have demonstrated efficacy and safety of immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma (mRCC). However, patients who do not meet trial eligibility criteria constitute a large proportion of the real-world population, and their outcomes remain poorly described.

PATIENTS AND METHODS: This nationwide, retrospective cohort study included all Danish patients with mRCC who initiated nivolumab plus ipilimumab (NIVO/IPI) by May 5, 2022. Clinical data were obtained from electronic patient records. Outcomes included median progression-free survival (mPFS), median overall survival (mOS), and objective response rate (ORR), assessed by treating physicians. Patients were classified as trial-eligible or ineligible according to CheckMate 214 (CM214) key criteria. Survival was estimated using Kaplan-Meier methods, and subgroups were explored.

RESULTS: A total of 464 patients were included, with a median follow-up of 33 months. In the total cohort, mPFS was 9 months, mOS 41 months, and ORR 43%, including 13% complete responses. Among 282 trial-eligible patients, outcomes were comparable to CM214 with mPFS 12 months and mOS 49 month, while 182 ineligible patients had inferior outcomes, with mPFS 6 months and mOS 26 months (both P < .001). The presence of brain metastases did not adversely affect OS, while patients with autoimmune disease demonstrated unexpectedly favorable outcomes. Severe treatment-related toxicity (≥ grade 3) occurred in 44% in the total cohort, comparable to CM214.

CONCLUSION: This is the first nationwide real-world study evaluating NIVO/IPI outcomes in unselected mRCC. Trial-eligible patients achieved survival outcomes comparable to clinical trial results. Although ineligible patients derived less benefit, they still experienced meaningful clinical outcomes. These findings provide benchmark data for treatment of real-world mRCC populations in routine clinical practice.

Original language	English
Article number	102450
Journal	Clinical Genitourinary Cancer
Volume	23
Issue number	6
Pages (from-to)	102450
ISSN	1938-0682
DOIs	https://doi.org/10.1016/j.clgc.2025.102450
Publication status	Published - Dec 2025

Keywords

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Carcinoma, Renal Cell/drug therapy
Denmark/epidemiology
Female
Humans
Immune Checkpoint Inhibitors/therapeutic use
Ipilimumab/administration & dosage
Kidney Neoplasms/drug therapy
Male
Middle Aged
Nivolumab/administration & dosage
Progression-Free Survival
Retrospective Studies
Treatment Outcome
Brain metastases outcomes
Immune checkpoint inhibitors
Trial ineligible patients
Autoimmune disease outcomes
Real-world evidence

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Jespersen, M. S., Palshof, J. A. E., Fristrup, N., Jensen, N. V., Henriksen, J. R., Iversen, A. B. B., Steen, S. G., Andersen, M., Madsen, K., Svane, I. M., & Darras, A. K. M. (2025). Nationwide Real-World Outcomes of Trial Eligible and Trial Ineligible Patients With Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab. Clinical Genitourinary Cancer, 23(6), 102450. Article 102450. https://doi.org/10.1016/j.clgc.2025.102450

Nationwide Real-World Outcomes of Trial Eligible and Trial Ineligible Patients With Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab. / Jespersen, Mette Syberg ; Palshof, Jesper Andreas Evers; Fristrup, Niels et al.
In: Clinical Genitourinary Cancer, Vol. 23, No. 6, 102450, 12.2025, p. 102450.

Research output: Contribution to journal › Journal article › Research › peer-review

Jespersen, MS , Palshof, JAE, Fristrup, N, Jensen, NV, Henriksen, JR, Iversen, ABB, Steen, SG, Andersen, M, Madsen, K , Svane, IM & Darras, AKM 2025, 'Nationwide Real-World Outcomes of Trial Eligible and Trial Ineligible Patients With Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab', Clinical Genitourinary Cancer, vol. 23, no. 6, 102450, pp. 102450. https://doi.org/10.1016/j.clgc.2025.102450

@article{00c45c4ea01344e0a6c59891b4a11be6,

title = "Nationwide Real-World Outcomes of Trial Eligible and Trial Ineligible Patients With Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab",

abstract = "INTRODUCTION: Clinical trials have demonstrated efficacy and safety of immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma (mRCC). However, patients who do not meet trial eligibility criteria constitute a large proportion of the real-world population, and their outcomes remain poorly described.PATIENTS AND METHODS: This nationwide, retrospective cohort study included all Danish patients with mRCC who initiated nivolumab plus ipilimumab (NIVO/IPI) by May 5, 2022. Clinical data were obtained from electronic patient records. Outcomes included median progression-free survival (mPFS), median overall survival (mOS), and objective response rate (ORR), assessed by treating physicians. Patients were classified as trial-eligible or ineligible according to CheckMate 214 (CM214) key criteria. Survival was estimated using Kaplan-Meier methods, and subgroups were explored.RESULTS: A total of 464 patients were included, with a median follow-up of 33 months. In the total cohort, mPFS was 9 months, mOS 41 months, and ORR 43\%, including 13\% complete responses. Among 282 trial-eligible patients, outcomes were comparable to CM214 with mPFS 12 months and mOS 49 month, while 182 ineligible patients had inferior outcomes, with mPFS 6 months and mOS 26 months (both P < .001). The presence of brain metastases did not adversely affect OS, while patients with autoimmune disease demonstrated unexpectedly favorable outcomes. Severe treatment-related toxicity (≥ grade 3) occurred in 44\% in the total cohort, comparable to CM214.CONCLUSION: This is the first nationwide real-world study evaluating NIVO/IPI outcomes in unselected mRCC. Trial-eligible patients achieved survival outcomes comparable to clinical trial results. Although ineligible patients derived less benefit, they still experienced meaningful clinical outcomes. These findings provide benchmark data for treatment of real-world mRCC populations in routine clinical practice.",

keywords = "Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Carcinoma, Renal Cell/drug therapy, Denmark/epidemiology, Female, Humans, Immune Checkpoint Inhibitors/therapeutic use, Ipilimumab/administration \& dosage, Kidney Neoplasms/drug therapy, Male, Middle Aged, Nivolumab/administration \& dosage, Progression-Free Survival, Retrospective Studies, Treatment Outcome, Brain metastases outcomes, Immune checkpoint inhibitors, Trial ineligible patients, Autoimmune disease outcomes, Real-world evidence",

author = "Jespersen, \{Mette Syberg\} and Palshof, \{Jesper Andreas Evers\} and Niels Fristrup and Jensen, \{Niels Viggo\} and Henriksen, \{Jon R{\o}ikj{\ae}r\} and Iversen, \{Ane Bundsb{\ae}k B{\o}ndergaard\} and Steen, \{Sarah Gr{\o}nbech\} and Morten Andersen and Kasper Madsen and Svane, \{Inge Marie\} and Darras, \{Anne Kirstine M{\o}ller\}",

year = "2025",

month = dec,

doi = "10.1016/j.clgc.2025.102450",

language = "English",

volume = "23",

pages = "102450",

journal = "Clinical Genitourinary Cancer",

issn = "1938-0682",

publisher = "Elsevier",

number = "6",

}

TY - JOUR

T1 - Nationwide Real-World Outcomes of Trial Eligible and Trial Ineligible Patients With Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab

AU - Jespersen, Mette Syberg

AU - Palshof, Jesper Andreas Evers

AU - Fristrup, Niels

AU - Jensen, Niels Viggo

AU - Henriksen, Jon Røikjær

AU - Iversen, Ane Bundsbæk Bøndergaard

AU - Steen, Sarah Grønbech

AU - Andersen, Morten

AU - Madsen, Kasper

AU - Svane, Inge Marie

AU - Darras, Anne Kirstine Møller

PY - 2025/12

Y1 - 2025/12

N2 - INTRODUCTION: Clinical trials have demonstrated efficacy and safety of immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma (mRCC). However, patients who do not meet trial eligibility criteria constitute a large proportion of the real-world population, and their outcomes remain poorly described.PATIENTS AND METHODS: This nationwide, retrospective cohort study included all Danish patients with mRCC who initiated nivolumab plus ipilimumab (NIVO/IPI) by May 5, 2022. Clinical data were obtained from electronic patient records. Outcomes included median progression-free survival (mPFS), median overall survival (mOS), and objective response rate (ORR), assessed by treating physicians. Patients were classified as trial-eligible or ineligible according to CheckMate 214 (CM214) key criteria. Survival was estimated using Kaplan-Meier methods, and subgroups were explored.RESULTS: A total of 464 patients were included, with a median follow-up of 33 months. In the total cohort, mPFS was 9 months, mOS 41 months, and ORR 43%, including 13% complete responses. Among 282 trial-eligible patients, outcomes were comparable to CM214 with mPFS 12 months and mOS 49 month, while 182 ineligible patients had inferior outcomes, with mPFS 6 months and mOS 26 months (both P < .001). The presence of brain metastases did not adversely affect OS, while patients with autoimmune disease demonstrated unexpectedly favorable outcomes. Severe treatment-related toxicity (≥ grade 3) occurred in 44% in the total cohort, comparable to CM214.CONCLUSION: This is the first nationwide real-world study evaluating NIVO/IPI outcomes in unselected mRCC. Trial-eligible patients achieved survival outcomes comparable to clinical trial results. Although ineligible patients derived less benefit, they still experienced meaningful clinical outcomes. These findings provide benchmark data for treatment of real-world mRCC populations in routine clinical practice.

AB - INTRODUCTION: Clinical trials have demonstrated efficacy and safety of immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma (mRCC). However, patients who do not meet trial eligibility criteria constitute a large proportion of the real-world population, and their outcomes remain poorly described.PATIENTS AND METHODS: This nationwide, retrospective cohort study included all Danish patients with mRCC who initiated nivolumab plus ipilimumab (NIVO/IPI) by May 5, 2022. Clinical data were obtained from electronic patient records. Outcomes included median progression-free survival (mPFS), median overall survival (mOS), and objective response rate (ORR), assessed by treating physicians. Patients were classified as trial-eligible or ineligible according to CheckMate 214 (CM214) key criteria. Survival was estimated using Kaplan-Meier methods, and subgroups were explored.RESULTS: A total of 464 patients were included, with a median follow-up of 33 months. In the total cohort, mPFS was 9 months, mOS 41 months, and ORR 43%, including 13% complete responses. Among 282 trial-eligible patients, outcomes were comparable to CM214 with mPFS 12 months and mOS 49 month, while 182 ineligible patients had inferior outcomes, with mPFS 6 months and mOS 26 months (both P < .001). The presence of brain metastases did not adversely affect OS, while patients with autoimmune disease demonstrated unexpectedly favorable outcomes. Severe treatment-related toxicity (≥ grade 3) occurred in 44% in the total cohort, comparable to CM214.CONCLUSION: This is the first nationwide real-world study evaluating NIVO/IPI outcomes in unselected mRCC. Trial-eligible patients achieved survival outcomes comparable to clinical trial results. Although ineligible patients derived less benefit, they still experienced meaningful clinical outcomes. These findings provide benchmark data for treatment of real-world mRCC populations in routine clinical practice.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Carcinoma, Renal Cell/drug therapy

KW - Denmark/epidemiology

KW - Female

KW - Humans

KW - Immune Checkpoint Inhibitors/therapeutic use

KW - Ipilimumab/administration & dosage

KW - Kidney Neoplasms/drug therapy

KW - Male

KW - Middle Aged

KW - Nivolumab/administration & dosage

KW - Progression-Free Survival

KW - Retrospective Studies

KW - Treatment Outcome

KW - Brain metastases outcomes

KW - Immune checkpoint inhibitors

KW - Trial ineligible patients

KW - Autoimmune disease outcomes

KW - Real-world evidence

UR - https://www.scopus.com/pages/publications/105022293621

U2 - 10.1016/j.clgc.2025.102450

DO - 10.1016/j.clgc.2025.102450

M3 - Journal article

C2 - 41176489

SN - 1938-0682

VL - 23

SP - 102450

JO - Clinical Genitourinary Cancer

JF - Clinical Genitourinary Cancer

IS - 6

M1 - 102450

ER -

Nationwide Real-World Outcomes of Trial Eligible and Trial Ineligible Patients With Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab

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Keywords

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