Clinical trial NCT02231749: Nivolumab Combined With Ipilimumab Versus Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 214)
Official title: A Phase 3, Randomized, Open-Label Study of Nivolumab Combined With Ipilimumab Versus Sunitinib Monotherapy in Subjects With Previously Untreated, Advanced or Metastatic Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Advanced Renal Cell Carcinoma
Metastatic Renal Cell Carcinoma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Ono Pharmaceutical Co. Ltd
First posted: 2014-09-04
Enrollment: 1390
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the objective response rate, progression free survival and the overall survival of Nivolumab combined with Ipilimumab to Sunitinib monotherapy in patients with previously untreated Renal Cell Cancer.


Eligibility criteria: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* Histological confirmation of renal cell carcinoma (RCC) with a clear-cell component
* Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC
* No prior systemic therapy for RCC with the following exception:

  1. One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets vascular endothelial growth factor (VEGF) or VEGF receptors and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy

     * Karnofsky Performance Status (KPS) of at least 70%
     * Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
     * Tumor tissue \[formalin-fixed paraffin-embedded (FFPE) archival or recent acquisition\] must be received by the central vendor (block or unstained slides) in order to randomize a subject to study treatment. (Note: Fine Needle Aspiration \[FNA\] and bone metastases samples are not acceptable for submission)

Exclusion Criteria:

* Any history of or current central nervous system (CNS) metastases. Baseline imaging of the brain is required within 28 days prior to randomization
* Prior systemic treatment with VEGF or VEGF receptor targeted therapy (including, but not limited to, Sunitinib, Pazopanib, Axitinib, Tivozanib, and Bevacizumab)
* Prior treatment with an anti-programmed death (PD)-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
* Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\>10 mg daily Prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
* Any condition requiring systemic treatment with corticosteroids (\>10 mg daily Prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses \>10 mg daily Prednisone equivalents are permitted in the absence of active autoimmune disease

Primary outcomes:
measure: Investigator-assessed Objective Response Rate(ORR) in Intermediate/Poor Risk Participants Per IRRC Using RECIST v1.1
timeFrame: From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (assessed up to June 2017, approximately 31 months)
measure: Overall Survival (OS) in Intermediate/Poor-Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)
timeFrame: From the date of randomization to the date of death (assessed up to June 2017, approximately 31 months)
measure: Progression-Free Survival (PFS) in Intermediate/Poor-Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)
timeFrame: From date of first dose to date of documented disease progression or death due to any cause, whichever occurs first (assessed up to June 2017, approximately 31 months)
Secondary outcomes:
measure: Investigator-assessed Objective Response Rate(ORR) in Any Risk Participants Per IRRC Using RECIST v1.1
timeFrame: From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (assessed up to June 2017, approximately 31 months)
measure: Overall Survival (OS) in Any Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)
timeFrame: From the date of randomization to the date of death (assessed up to June 2017, approximately 31 months)
measure: Progression-Free Survival (PFS) in Any Risk Participants With Previously Untreated Metastatic Renal Cell Carcinoma (mRCC)
timeFrame: From date of first dose to date of documented disease progression or death due to any cause, whichever occurs first (assessed up to June 2017, approximately 31 months)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Local Institution - 0006
state: California
city: La Jolla
country: United States
facility: Local Institution - 0057
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0044
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0035
state: California
city: Stanford
country: United States
facility: Local Institution - 0067
state: California
city: New Haven
country: United States
facility: Local Institution - 0138
state: Connecticut
city: Washington
country: United States
facility: Local Institution - 0034
state: District of Columbia
city: Tampa
country: United States
facility: Local Institution - 0049
state: Florida
city: Atlanta
country: United States
facility: Local Institution - 0068
state: Georgia
city: Indianapolis
country: United States
facility: Local Institution - 0038
state: Indiana
city: Iowa City
country: United States
facility: Local Institution - 0042
state: Iowa
city: Fairway
country: United States
facility: Local Institution - 0163
state: Kansas
city: Baltimore
country: United States
facility: Local Institution - 0048
state: Maryland
city: Baltimore
country: United States
facility: Local Institution - 0004
state: Maryland
city: Boston
country: United States
facility: Local Institution - 0135
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0110
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0161
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0173
state: Massachusetts
city: Ann Arbor
country: United States
facility: Local Institution - 0046
state: Michigan
city: Detroit
country: United States
facility: Local Institution - 0043
state: Michigan
city: Buffalo
country: United States
facility: Local Institution - 0036
state: New York
city: New York
country: United States
facility: Local Institution - 0001
state: New York
city: Charlotte
country: United States
facility: Local Institution - 0008
state: North Carolina
city: Durham
country: United States
facility: Local Institution - 0045
state: North Carolina
city: Cleveland
country: United States
facility: Local Institution - 0007
state: Ohio
city: Columbus
country: United States
facility: Local Institution - 0164
state: Ohio
city: Portland
country: United States
facility: Local Institution - 0039
state: Oregon
city: Allentown
country: United States
facility: Local Institution - 0054
state: Pennsylvania
city: Philadelphia
country: United States
facility: Local Institution - 0005
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Local Institution - 0031
state: Pennsylvania
city: Charleston
country: United States
facility: Local Institution - 0055
state: South Carolina
city: Chattanooga
country: United States
facility: Local Institution - 0159
state: Tennessee
city: Nashville
country: United States
facility: Local Institution - 0066
state: Tennessee
city: Dallas
country: United States
facility: Local Institution - 0056
state: Texas
city: Dallas
country: United States
facility: Local Institution - 0032
state: Texas
city: Houston
country: United States
facility: Local Institution - 0003
state: Texas
city: Seattle
country: United States
facility: Local Institution - 0041
state: Washington
city: Berazategui
country: Argentina
facility: Local Institution - 0099
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution - 0098
state: Buenos Aires
city: Ciudad Autonoma De Buenos Aire
country: Argentina
facility: Local Institution - 0139
state: Buenos Aires
city: San Miguel De Tucuman
country: Argentina
facility: Local Institution - 0095
state: Tucuman
city: San Miguel de Tucuman
country: Argentina
facility: Local Institution - 0096
state: Tucuman
city: Caba
country: Argentina
facility: Local Institution - 0097
city: Cordoba
country: Argentina
facility: Local Institution - 0100
city: Kogarah
country: Australia
facility: Local Institution - 0073
state: New South Wales
city: Westmead
country: Australia
facility: Local Institution - 0070
state: New South Wales
city: Herston
country: Australia
facility: Local Institution - 0076
state: Queensland
city: Southport
country: Australia
facility: Local Institution - 0075
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Local Institution - 0140
state: South Australia
city: Box Hill
country: Australia
facility: Local Institution - 0072
state: Victoria
city: Clayton
country: Australia
facility: Local Institution - 0071
state: Victoria
city: Nedlands
country: Australia
facility: Local Institution - 0104
state: Western Australia
city: Murdoch
country: Australia
facility: Local Institution - 0074
city: Linz
country: Austria
facility: Local Institution - 0108
city: Wels
country: Austria
facility: Local Institution - 0107
city: Wien
country: Austria
facility: Local Institution - 0109
city: Gent
country: Belgium
facility: Local Institution - 0020
city: Leuven
country: Belgium
facility: Local Institution - 0019
city: Belo Horizonte
country: Brazil
facility: Local Institution - 0152
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Local Institution - 0150
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Local Institution - 0151
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Local Institution - 0153
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Local Institution - 0157
city: Sao Paulo
country: Brazil
facility: Local Institution - 0155
city: Sao Paulo
country: Brazil
facility: Local Institution - 0156
city: Calgary
country: Canada
facility: Local Institution - 0149
state: Alberta
city: Edmonton
country: Canada
facility: Local Institution - 0133
state: Alberta
city: Kelowna
country: Canada
facility: Local Institution - 0182
state: British Columbia
city: Vancouver
country: Canada
facility: Local Institution - 0128
state: British Columbia
city: Moncton
country: Canada
facility: Local Institution - 0131
state: New Brunswick
city: Toronto
country: Canada
facility: Local Institution - 0172
state: Ontario
city: Toronto
country: Canada
facility: Local Institution - 0148
state: Ontario
city: Montreal
country: Canada
facility: Local Institution - 0132
state: Quebec
city: Santiago
country: Chile
facility: Local Institution - 0102
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution - 0144
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution - 0101
state: Región Metropolitana De Santiago
city: Vina del Mar
country: Chile
facility: Local Institution - 0103
city: Bogota
country: Colombia
facility: Local Institution - 0080
city: Medellin
country: Colombia
facility: Local Institution - 0162
city: Medellin
country: Colombia
facility: Local Institution - 0081
city: Liberec
country: Czechia
facility: Local Institution - 0050
state: Liberecký Kraj
city: Brno
country: Czechia
facility: Local Institution - 0053
city: Hradec Kralove
country: Czechia
facility: Local Institution - 0051
city: Olomouc
country: Czechia
facility: Local Institution - 0052
city: Aarhus N
country: Denmark
facility: Local Institution - 0136
state: Midtjylland
city: Herlev
country: Denmark
facility: Local Institution - 0158
city: Odense
country: Denmark
facility: Local Institution - 0137
city: Helsinki
country: Finland
facility: Local Institution - 0027
state: Uusimaa
city: Tampere
country: Finland
facility: Local Institution - 0028
city: Besançon
country: France
facility: Local Institution - 0170
city: Bordeaux
country: France
facility: Local Institution - 0062
city: La Roche-Sur-Yon Cedex 9
country: France
facility: Local Institution - 0169
city: Marseille Cedex 9
country: France
facility: Local Institution - 0060
city: Saint Herblain
country: France
facility: Local Institution - 0063
city: Strasbourg
country: France
facility: Local Institution - 0065
city: Toulouse Cedex 9
country: France
facility: Local Institution - 0059
city: Villejuif
country: France
facility: Local Institution - 0058
city: Paris
country: France
facility: Local Institution - 0061
state: Île-de-France
city: Aachen
country: Germany
facility: Local Institution - 0125
city: Erlangen
country: Germany
facility: Local Institution - 0126
city: Frankfurt
country: Germany
facility: Local Institution - 0141
city: Hamburg
country: Germany
facility: Local Institution - 0147
city: Hannover
country: Germany
facility: Local Institution - 0142
city: Heidelberg
country: Germany
facility: Local Institution - 0123
city: Homburg
country: Germany
facility: Local Institution - 0127
city: Jena
country: Germany
facility: Local Institution - 0129
city: Magdeburg
country: Germany
facility: Local Institution - 0143
city: Muenchen
country: Germany
facility: Local Institution - 0124
city: Muenster
country: Germany
facility: Local Institution - 0146
city: Ulm
country: Germany
facility: Local Institution - 0130
city: Gyula
country: Hungary
facility: Local Institution - 0184
state: Békés
city: Budapest
country: Hungary
facility: Local Institution - 0083
city: Debrecen
country: Hungary
facility: Local Institution - 0082
city: Pecs
country: Hungary
facility: Local Institution - 0084
city: Wilton
country: Ireland
facility: Local Institution - 0015
state: Cork
city: Dublin 7
country: Ireland
facility: Local Institution - 0017
state: Dublin
city: Dublin 7
country: Ireland
facility: Local Institution - 0018
state: Dublin
city: Dublin
country: Ireland
facility: Local Institution - 0016
city: Haifa
country: Israel
facility: Local Institution - 0120
city: Kfar Saba
country: Israel
facility: Local Institution - 0117
city: Petach Tikva
country: Israel
facility: Local Institution - 0121
city: Ramat-gan
country: Israel
facility: Local Institution - 0118
city: Zerifin
country: Israel
facility: Local Institution - 0119
city: Arezzo
country: Italy
facility: Local Institution - 0022
city: Meldola (fc)
country: Italy
facility: Local Institution - 0024
city: Milano
country: Italy
facility: Local Institution - 0023
city: Napoli
country: Italy
facility: Local Institution - 0064
city: Padova
country: Italy
facility: Local Institution - 0079
city: Pavia
country: Italy
facility: Local Institution - 0025
city: Roma
country: Italy
facility: Local Institution - 0026
city: Akita-shi
country: Japan
facility: Local Institution - 0192
state: Akita
city: Hirosaki
country: Japan
facility: Local Institution - 0209
state: Aomori
city: Chiba-shi
country: Japan
facility: Local Institution - 0187
state: Chiba
city: Fukuoka-shi
country: Japan
facility: Local Institution - 0196
state: Fukuoka
city: Sapporo-shi
country: Japan
facility: Local Institution - 0188
state: Hokai-do
city: Sapporo
country: Japan
facility: Local Institution - 0183
state: Hokkaido
city: Kobe
country: Japan
facility: Local Institution - 0206
state: Hyogo
city: Tsukuba-shi
country: Japan
facility: Local Institution - 0205
state: Ibaraki
city: Morioka-shi
country: Japan
facility: Local Institution - 0200
state: Iwate
city: Yokohama-shi
country: Japan
facility: Local Institution - 0186
state: Kanagawa
city: Kumamoto-shi
country: Japan
facility: Local Institution - 0189
state: Kumamoto
city: Kyoto-shi
country: Japan
facility: Local Institution - 0191
state: Kyoto
city: Niigata-shi
country: Japan
facility: Local Institution - 0199
state: Niigata
city: Okayama-shi
country: Japan
facility: Local Institution - 0204
state: Okayama
city: Osakasayamashi
country: Japan
facility: Local Institution - 0190
state: Osaka
city: Suita-shi
country: Japan
facility: Local Institution - 0201
state: Osaka
city: Hamamatsu-shi
country: Japan
facility: Local Institution - 0208
state: Shizuoka
city: Tokushima-shi
country: Japan
facility: Local Institution - 0194
state: Tokushima
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0202
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0197
state: Tokyo
city: Bunkyo-ku
country: Japan
facility: Local Institution - 0195
state: Tokyo
city: Koto-ku
country: Japan
facility: Local Institution - 0207
state: Tokyo
city: Shinjuku-Ku
country: Japan
facility: Local Institution - 0185
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Local Institution - 0193
state: Tokyo
city: Tokyo
country: Japan
facility: Local Institution - 0198
city: Yamagata
country: Japan
facility: Local Institution - 0203
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0178
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0177
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0176
city: Mexico D.f.
country: Mexico
facility: Local Institution - 0168
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Local Institution - 0171
state: Nuevo Leon
city: Queretaro
country: Mexico
facility: Local Institution - 0175
state: Querétaro
city: Oaxaca
country: Mexico
facility: Local Institution - 0167
city: Amsterdam
country: Netherlands
facility: Local Institution - 0029
state: Noord-Holland
city: Groningen
country: Netherlands
facility: Local Institution - 0040
city: Nijmegen
country: Netherlands
facility: Local Institution - 0030
city: Krakow
country: Poland
facility: Local Institution - 0093
city: Poznan
country: Poland
facility: Local Institution - 0112
city: Wroclaw
country: Poland
facility: Local Institution - 0106
city: Barcelona
country: Spain
facility: Local Institution - 0089
city: Barcelona
country: Spain
facility: Local Institution - 0088
city: Madrid
country: Spain
facility: Local Institution - 0086
city: Madrid
country: Spain
facility: Local Institution - 0085
city: Madrid
country: Spain
facility: Local Institution - 0087
city: Oviedo
country: Spain
facility: Local Institution - 0111
city: Sevilla
country: Spain
facility: Local Institution - 0090
city: Stockholm
country: Sweden
facility: Local Institution - 0134
city: Taipei
country: Taiwan
facility: Local Institution - 0179
city: Taipei
country: Taiwan
facility: Local Institution - 0180
city: Taoyuan
country: Taiwan
facility: Local Institution - 0181
city: Ankara
country: Turkey
facility: Local Institution - 0115
city: Antalya
country: Turkey
facility: Local Institution - 0114
city: Istanbul
country: Turkey
facility: Local Institution - 0122
city: London
country: United Kingdom
facility: Local Institution - 0010
state: Greater London
city: Glasgow
country: United Kingdom
facility: Local Institution - 0009
state: Lanarkshire
city: London
country: United Kingdom
facility: Local Institution - 0077
city: Manchester
country: United Kingdom
facility: Local Institution - 0021
city: Northwood
country: United Kingdom
facility: Local Institution - 0011
city: Swansea
country: United Kingdom
facility: Local Institution - 0012
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Motzer RJ, McDermott DF, Escudier B, Burotto M, Choueiri TK, Hammers HJ, Barthelemy P, Plimack ER, Porta C, George S, Powles T, Donskov F, Gurney H, Kollmannsberger CK, Grimm MO, Barrios C, Tomita Y, Castellano D, Grunwald V, Rini BI, McHenry MB, Lee CW, McCarthy J, Ejzykowicz F, Tannir NM. Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma. Cancer. 2022 Jun 1;128(11):2085-2097. doi: 10.1002/cncr.34180. Epub 2022 Apr 5.
citation: Labriola MK, George DJ. Setting a new standard for long-term survival in metastatic kidney cancer. Cancer. 2022 Jun 1;128(11):2058-2060. doi: 10.1002/cncr.34177. Epub 2022 Apr 5. No abstract available.
citation: Albiges L, Tannir NM, Burotto M, McDermott D, Plimack ER, Barthelemy P, Porta C, Powles T, Donskov F, George S, Kollmannsberger CK, Gurney H, Grimm MO, Tomita Y, Castellano D, Rini BI, Choueiri TK, Leung D, Saggi SS, Lee CW, McHenry MB, Motzer RJ. First-line Nivolumab plus Ipilimumab Versus Sunitinib in Patients Without Nephrectomy and With an Evaluable Primary Renal Tumor in the CheckMate 214 Trial. Eur Urol. 2022 Mar;81(3):266-271. doi: 10.1016/j.eururo.2021.10.001. Epub 2021 Nov 5.
citation: Albiges L, Tannir NM, Burotto M, McDermott D, Plimack ER, Barthelemy P, Porta C, Powles T, Donskov F, George S, Kollmannsberger CK, Gurney H, Grimm MO, Tomita Y, Castellano D, Rini BI, Choueiri TK, Saggi SS, McHenry MB, Motzer RJ. Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO Open. 2020 Nov;5(6):e001079. doi: 10.1136/esmoopen-2020-001079.
citation: Motzer RJ, Escudier B, McDermott DF, Aren Frontera O, Melichar B, Powles T, Donskov F, Plimack ER, Barthelemy P, Hammers HJ, George S, Grunwald V, Porta C, Neiman V, Ravaud A, Choueiri TK, Rini BI, Salman P, Kollmannsberger CK, Tykodi SS, Grimm MO, Gurney H, Leibowitz-Amit R, Geertsen PF, Amin A, Tomita Y, McHenry MB, Saggi SS, Tannir NM. Survival outcomes and independent response assessment with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma: 42-month follow-up of a randomized phase 3 clinical trial. J Immunother Cancer. 2020 Jul;8(2):e000891. doi: 10.1136/jitc-2020-000891.
citation: Ambavane A, Yang S, Atkins MB, Rao S, Shah A, Regan MM, McDermott DF, Michaelson MD. Clinical and economic outcomes of treatment sequences for intermediate- to poor-risk advanced renal cell carcinoma. Immunotherapy. 2020 Jan;12(1):37-51. doi: 10.2217/imt-2019-0199. Epub 2020 Jan 29.
citation: Tomita Y, Kondo T, Kimura G, Inoue T, Wakumoto Y, Yao M, Sugiyama T, Oya M, Fujii Y, Obara W, Motzer RJ, Uemura H. Nivolumab plus ipilimumab versus sunitinib in previously untreated advanced renal-cell carcinoma: analysis of Japanese patients in CheckMate 214 with extended follow-up. Jpn J Clin Oncol. 2020 Jan 24;50(1):12-19. doi: 10.1093/jjco/hyz132.
citation: Motzer RJ, Rini BI, McDermott DF, Aren Frontera O, Hammers HJ, Carducci MA, Salman P, Escudier B, Beuselinck B, Amin A, Porta C, George S, Neiman V, Bracarda S, Tykodi SS, Barthelemy P, Leibowitz-Amit R, Plimack ER, Oosting SF, Redman B, Melichar B, Powles T, Nathan P, Oudard S, Pook D, Choueiri TK, Donskov F, Grimm MO, Gurney H, Heng DYC, Kollmannsberger CK, Harrison MR, Tomita Y, Duran I, Grunwald V, McHenry MB, Mekan S, Tannir NM; CheckMate 214 investigators. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol. 2019 Oct;20(10):1370-1385. doi: 10.1016/S1470-2045(19)30413-9. Epub 2019 Aug 16.
citation: Cella D, Grunwald V, Escudier B, Hammers HJ, George S, Nathan P, Grimm MO, Rini BI, Doan J, Ivanescu C, Paty J, Mekan S, Motzer RJ. Patient-reported outcomes of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib (CheckMate 214): a randomised, phase 3 trial. Lancet Oncol. 2019 Feb;20(2):297-310. doi: 10.1016/S1470-2045(18)30778-2. Epub 2019 Jan 15.
citation: Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthelemy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B; CheckMate 214 Investigators. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21.