CheckMate 025 Randomized Phase 3 Study

Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma [Figure presented]

on behalf of the CheckMate 025 investigators

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Background The randomized, phase 3 CheckMate 025 study of nivolumab (n = 410) versus everolimus (n = 411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). Objective To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus. Design, setting, and participants Subgroup OS analyses were performed using Kaplan-Meier methodology. Hazard ratios were estimated using the Cox proportional hazards model. Intervention Nivolumab 3 mg/kg every 2 wk or everolimus 10 mg once daily. Results and limitations The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age <65 and ≥65 yr; one and two or more sites of metastases; bone, liver, and lung metastases; number of prior therapies; duration of prior therapy; and prior sunitinib, pazopanib, or interleukin-2 therapy. The benefit with nivolumab versus everolimus was noteworthy for patients with poor MSKCC risk (hazard ratio 0.48, 95% confidence interval 0.32–0.70). The mortality rate at 12 mo for all subgroups was lower with nivolumab compared with everolimus. ORR also favored nivolumab. The incidence of grade 3 or 4 treatment-related adverse events across subgroups was lower with nivolumab. Limitations include the post hoc analysis and differing sample sizes between groups. Conclusion The trend for OS and ORR benefit with nivolumab for multiple subgroups, without notable safety concerns, may help to guide treatment decisions, and further supports nivolumab as the standard of care in previously treated patients with aRCC. Patient summary We investigated the impact of demographic and pretreatment features on survival benefit and tumor response with nivolumab versus everolimus in advanced renal cell carcinoma (aRCC). Survival benefit and response were observed for multiple subgroups, supporting the use of nivolumab as a new standard of care across a broad range of patients with previously treated aRCC. The trial is registered on ClinicalTrials.gov as NCT01668784. Consistent with the benefit demonstrated in previously treated patients with advanced renal cell carcinoma from CheckMate 025, an overall survival and objective response rate benefit with nivolumab versus everolimus was observed for multiple subgroups, including prognostic risk categories, age, number and sites of metastases, and prior therapies.

Original languageEnglish (US)
Pages (from-to)962-971
Number of pages10
JournalEuropean Urology
Volume72
Issue number6
DOIs
StatePublished - Dec 1 2017

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Renal Cell Carcinoma
Outcome Assessment (Health Care)
Survival
Therapeutics
Standard of Care
Neoplasm Metastasis
nivolumab
Everolimus
Neoplasms
Survival Analysis
Proportional Hazards Models
Sample Size
Interleukin-2
Odds Ratio
Demography
Databases
Confidence Intervals

Keywords

  • Everolimus
  • Immune checkpoint inhibitor
  • Nivolumab
  • Phase 3
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Urology

Cite this

CheckMate 025 Randomized Phase 3 Study : Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma [Figure presented]. / on behalf of the CheckMate 025 investigators.

In: European Urology, Vol. 72, No. 6, 01.12.2017, p. 962-971.

Research output: Contribution to journalArticle

@article{7520d61adb504a8c9297344d50b4064e,
title = "CheckMate 025 Randomized Phase 3 Study: Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma [Figure presented]",
abstract = "Background The randomized, phase 3 CheckMate 025 study of nivolumab (n = 410) versus everolimus (n = 411) in previously treated adults (75{\%} male; 88{\%} white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). Objective To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus. Design, setting, and participants Subgroup OS analyses were performed using Kaplan-Meier methodology. Hazard ratios were estimated using the Cox proportional hazards model. Intervention Nivolumab 3 mg/kg every 2 wk or everolimus 10 mg once daily. Results and limitations The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age <65 and ≥65 yr; one and two or more sites of metastases; bone, liver, and lung metastases; number of prior therapies; duration of prior therapy; and prior sunitinib, pazopanib, or interleukin-2 therapy. The benefit with nivolumab versus everolimus was noteworthy for patients with poor MSKCC risk (hazard ratio 0.48, 95{\%} confidence interval 0.32–0.70). The mortality rate at 12 mo for all subgroups was lower with nivolumab compared with everolimus. ORR also favored nivolumab. The incidence of grade 3 or 4 treatment-related adverse events across subgroups was lower with nivolumab. Limitations include the post hoc analysis and differing sample sizes between groups. Conclusion The trend for OS and ORR benefit with nivolumab for multiple subgroups, without notable safety concerns, may help to guide treatment decisions, and further supports nivolumab as the standard of care in previously treated patients with aRCC. Patient summary We investigated the impact of demographic and pretreatment features on survival benefit and tumor response with nivolumab versus everolimus in advanced renal cell carcinoma (aRCC). Survival benefit and response were observed for multiple subgroups, supporting the use of nivolumab as a new standard of care across a broad range of patients with previously treated aRCC. The trial is registered on ClinicalTrials.gov as NCT01668784. Consistent with the benefit demonstrated in previously treated patients with advanced renal cell carcinoma from CheckMate 025, an overall survival and objective response rate benefit with nivolumab versus everolimus was observed for multiple subgroups, including prognostic risk categories, age, number and sites of metastases, and prior therapies.",
keywords = "Everolimus, Immune checkpoint inhibitor, Nivolumab, Phase 3, Renal cell carcinoma",
author = "{on behalf of the CheckMate 025 investigators} and Bernard Escudier and Padmanee Sharma and McDermott, {David F.} and Saby George and Hammers, {Hans J.} and Sandhya Srinivas and Tykodi, {Scott S.} and Sosman, {Jeffrey A.} and Giuseppe Procopio and Plimack, {Elizabeth R.} and Daniel Castellano and Howard Gurney and Frede Donskov and Katriina Peltola and John Wagstaff and Gauler, {Thomas C.} and Takeshi Ueda and Huanyu Zhao and Waxman, {Ian M.} and Motzer, {Robert J.}",
year = "2017",
month = "12",
day = "1",
doi = "10.1016/j.eururo.2017.02.010",
language = "English (US)",
volume = "72",
pages = "962--971",
journal = "European Urology",
issn = "0302-2838",
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TY - JOUR

T1 - CheckMate 025 Randomized Phase 3 Study

T2 - Outcomes by Key Baseline Factors and Prior Therapy for Nivolumab Versus Everolimus in Advanced Renal Cell Carcinoma [Figure presented]

AU - on behalf of the CheckMate 025 investigators

AU - Escudier, Bernard

AU - Sharma, Padmanee

AU - McDermott, David F.

AU - George, Saby

AU - Hammers, Hans J.

AU - Srinivas, Sandhya

AU - Tykodi, Scott S.

AU - Sosman, Jeffrey A.

AU - Procopio, Giuseppe

AU - Plimack, Elizabeth R.

AU - Castellano, Daniel

AU - Gurney, Howard

AU - Donskov, Frede

AU - Peltola, Katriina

AU - Wagstaff, John

AU - Gauler, Thomas C.

AU - Ueda, Takeshi

AU - Zhao, Huanyu

AU - Waxman, Ian M.

AU - Motzer, Robert J.

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Background The randomized, phase 3 CheckMate 025 study of nivolumab (n = 410) versus everolimus (n = 411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). Objective To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus. Design, setting, and participants Subgroup OS analyses were performed using Kaplan-Meier methodology. Hazard ratios were estimated using the Cox proportional hazards model. Intervention Nivolumab 3 mg/kg every 2 wk or everolimus 10 mg once daily. Results and limitations The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age <65 and ≥65 yr; one and two or more sites of metastases; bone, liver, and lung metastases; number of prior therapies; duration of prior therapy; and prior sunitinib, pazopanib, or interleukin-2 therapy. The benefit with nivolumab versus everolimus was noteworthy for patients with poor MSKCC risk (hazard ratio 0.48, 95% confidence interval 0.32–0.70). The mortality rate at 12 mo for all subgroups was lower with nivolumab compared with everolimus. ORR also favored nivolumab. The incidence of grade 3 or 4 treatment-related adverse events across subgroups was lower with nivolumab. Limitations include the post hoc analysis and differing sample sizes between groups. Conclusion The trend for OS and ORR benefit with nivolumab for multiple subgroups, without notable safety concerns, may help to guide treatment decisions, and further supports nivolumab as the standard of care in previously treated patients with aRCC. Patient summary We investigated the impact of demographic and pretreatment features on survival benefit and tumor response with nivolumab versus everolimus in advanced renal cell carcinoma (aRCC). Survival benefit and response were observed for multiple subgroups, supporting the use of nivolumab as a new standard of care across a broad range of patients with previously treated aRCC. The trial is registered on ClinicalTrials.gov as NCT01668784. Consistent with the benefit demonstrated in previously treated patients with advanced renal cell carcinoma from CheckMate 025, an overall survival and objective response rate benefit with nivolumab versus everolimus was observed for multiple subgroups, including prognostic risk categories, age, number and sites of metastases, and prior therapies.

AB - Background The randomized, phase 3 CheckMate 025 study of nivolumab (n = 410) versus everolimus (n = 411) in previously treated adults (75% male; 88% white) with advanced renal cell carcinoma (aRCC) demonstrated significantly improved overall survival (OS) and objective response rate (ORR). Objective To investigate which baseline factors were associated with OS and ORR benefit with nivolumab versus everolimus. Design, setting, and participants Subgroup OS analyses were performed using Kaplan-Meier methodology. Hazard ratios were estimated using the Cox proportional hazards model. Intervention Nivolumab 3 mg/kg every 2 wk or everolimus 10 mg once daily. Results and limitations The minimum follow-up was 14 mo. Baseline subgroup distributions were balanced between nivolumab and everolimus arms. Nivolumab demonstrated an OS improvement versus everolimus across subgroups, including Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium risk groups; age <65 and ≥65 yr; one and two or more sites of metastases; bone, liver, and lung metastases; number of prior therapies; duration of prior therapy; and prior sunitinib, pazopanib, or interleukin-2 therapy. The benefit with nivolumab versus everolimus was noteworthy for patients with poor MSKCC risk (hazard ratio 0.48, 95% confidence interval 0.32–0.70). The mortality rate at 12 mo for all subgroups was lower with nivolumab compared with everolimus. ORR also favored nivolumab. The incidence of grade 3 or 4 treatment-related adverse events across subgroups was lower with nivolumab. Limitations include the post hoc analysis and differing sample sizes between groups. Conclusion The trend for OS and ORR benefit with nivolumab for multiple subgroups, without notable safety concerns, may help to guide treatment decisions, and further supports nivolumab as the standard of care in previously treated patients with aRCC. Patient summary We investigated the impact of demographic and pretreatment features on survival benefit and tumor response with nivolumab versus everolimus in advanced renal cell carcinoma (aRCC). Survival benefit and response were observed for multiple subgroups, supporting the use of nivolumab as a new standard of care across a broad range of patients with previously treated aRCC. The trial is registered on ClinicalTrials.gov as NCT01668784. Consistent with the benefit demonstrated in previously treated patients with advanced renal cell carcinoma from CheckMate 025, an overall survival and objective response rate benefit with nivolumab versus everolimus was observed for multiple subgroups, including prognostic risk categories, age, number and sites of metastases, and prior therapies.

KW - Everolimus

KW - Immune checkpoint inhibitor

KW - Nivolumab

KW - Phase 3

KW - Renal cell carcinoma

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