661P - Conditional survival and 5-year follow-up in CheckMate 214: First-line nivolumab + ipilimumab (N+I) versus sunitinib (S) in advanced renal cell carcinoma (aRCC)

Background

Conditional survival, used to predict sustained treatment benefit, accounts for time since treatment initiation and provides improved prognostic information at landmark time points. Conditional survival in aRCC patients (pts) was estimated in CheckMate 214 with a minimum 5-y follow-up (median follow-up, 67.7 mo).

Methods

Pts with clear cell aRCC were randomized to N 3 mg/kg + I 1 mg/kg Q3W×4 then N 3 mg/kg Q2W vs S 50 mg QD for 4 wk on, 2 wk off. Trial endpoints included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR; both per independent radiology review using RECIST v1.1) in IMDC intermediate/poor risk (IP; primary), intent-to-treat (ITT; secondary), and favorable risk (FAV; exploratory) pts. Conditional survival—the probability of remaining alive (cOS), progression-free (cPFS), or in response (cDOR) 2 y beyond landmark time points of 2 y and 3 y—was analyzed.

Results

Superior OS, PFS, ORR and complete response (CR) benefits with N+I vs S were maintained in ITT and IP pts and are summarized together with outcomes in FAV pts (Table). Consistently higher cOS, cPFS, and cDOR rates were observed with N+I vs S in ITT and IP pts at all time points (Table). In the N+I arm, the probability of remaining alive 2 y beyond the 3-y landmark (cOS) was 81% (ITT), 79% (IP), and 85% (FAV). The probability of remaining progression-free (cPFS) for an additional 2 y beyond the 3-y landmark was 89% (ITT), 90% (IP), and 85% (FAV). For N+I pts who were in response at 3 y, the probability of remaining in response (cDOR) for an additional 2 y was 89% (ITT), 90% (IP), and 85% (FAV). No new safety signals emerged with longer follow-up. Table: 661P

^an = pts alive, progression free, or in response at each time point (data not shown). DOR, duration of response; NR, not reached.

Conclusions

Long-term follow-up in this 5-y analysis demonstrated durable efficacy benefits with N+I vs S. Conditional survival results predict increased probability of durable OS, PFS, and response with N+I at 2-y and 3-y landmarks, and highlight the long-term clinical benefit with N+I in pts with aRCC.

Clinical trial identification

NCT02231749.

Editorial acknowledgement

Professional medical writing assistance was provided by Rachel Maddente, PhD, of Parexel, funded by Bristol Myers Squibb Company.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb Company (Princeton, NJ) and ONO Pharmaceutical Company Ltd. (Osaka, Japan).

Disclosure

R.J. Motzer: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Genentech/Roche; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Lilly Oncology; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Aveo Pharmaceuticals; Financial Interests, Institutional, Invited Speaker, funding for trial conduct from sponsor to my employer MSKCC: Pfizer; Financial Interests, Institutional, Invited Speaker, funding for trial conduct from sponsor to my employer MSKCC: Eisai; Financial Interests, Institutional, Invited Speaker, funding for trial conduct from sponsor to my employer MSKCC: Genentech/Roche; Financial Interests, Institutional, Invited Speaker, funding for trial conduct from sponsor to my employer MSKCC: Merck; Financial Interests, Institutional, Invited Speaker, funding for trial conduct from sponsor to my employer MSKCC: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker, funding for trial conduct from sponsor to my employer MSKCC: Exelixis. N.M. Tannir: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Nektar Therapeutics; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Eisai Medical; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Oncorena; Financial Interests, Personal, Advisory Board: Calithera Bioscience; Financial Interests, Personal, Advisory Board: Surface Oncology; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Calithera Bioscience; Financial Interests, Institutional, Research Grant: Arrowhead Pharmaceuticals, Inc. D.F. McDermott: Financial Interests, Personal, Other, Consultant: BMS; Financial Interests, Personal, Other, Consultant: Pfizer; Financial Interests, Personal, Other, Consultant: Merck; Financial Interests, Personal, Other, Consultant: Alkermes, Inc; Financial Interests, Personal, Other, Consultant: EMD Serono; Financial Interests, Personal, Other, Consultant: Eli Lilly and Company; Financial Interests, Personal, Other, Consultant: Iovance; Financial Interests, Personal, Other, Consultant: Eisai Inc.; Financial Interests, Personal, Other, Consultant: Werewolf Therapeutics; Financial Interests, Personal, Other, Consultant: Calithera Biosciences; Financial Interests, Personal, Research Grant, Cancer Research: BMS; Financial Interests, Personal, Research Grant, Cancer Research: Merck; Financial Interests, Personal, Research Grant, Cancer Research: Genentech; Financial Interests, Personal, Research Grant, Cancer Research: Pfizer; Financial Interests, Personal, Research Grant, Cancer Research: Exelixis; Financial Interests, Personal, Research Grant, Cancer Research: X4 Pharma; Financial Interests, Personal, Research Grant, Cancer Research: Alkermes, Inc. M. Burotto: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Novartis. T.K. Choueiri: Financial Interests, Personal, Invited Speaker, Best of ASCO19 talk: Advent Health; Financial Interests, Personal, Other, Consultant on onc drugs: Analysis Group; Financial Interests, Personal, Advisory Board, Advising oncology strategy: Aptitude Health; Financial Interests, Personal, Invited Speaker, ASCO-related event: ASCO-SITC; Financial Interests, Personal, Invited Speaker, CME, ImmunoOncology in RCC: ASiM, CE; Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: AstraZeneca; Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: BMS; Financial Interests, Personal, Advisory Board, Advice on RCC drug: Calithera; Financial Interests, Personal, Invited Speaker, RCC webinar: Cancernet; Financial Interests, Personal, Invited Speaker, CME,PodCast in RCC ($500.00): Caribou Publishing; Financial Interests, Personal, Advisory Board, Advice on onc drugson Onc drugs: EMD Serono; Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: Exelixis; Financial Interests, Personal, Invited Speaker, CME, Kidney Cancer Association ($1300): France Foundation; Financial Interests, Personal, Advisory Board, Advice on Onc Drugs: Infinity; Financial Interests, Personal, Invited Speaker, RCC Drug: Ipsen; Financial Interests, Personal, Invited Speaker, Reimbursement ($432.00): Kidney Cancer Association; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker, Grand Rounds: MDACC; Financial Interests, Personal, Advisory Board, Advice on GU-RCC drugs: Merck; Financial Interests, Personal, Invited Speaker, CME,mjhlifesciences.com: MJH life sciences; Financial Interests, Personal, Invited Speaker, National Associatiion of Managed Care: NAMC; Financial Interests, Personal, Other, Grant review to Orien Network: ORIEN; Financial Interests, Personal, Invited Speaker, CME, www.peerview.com: Peerview; Financial Interests, Personal, Invited Speaker, CME, gotoper.com: PER; Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: Pfizer; Financial Interests, Personal, Invited Speaker, CME, researchtopractice.com: ResearchToPractice; Financial Interests, Personal, Invited Speaker, CME, RCC: Springer; Financial Interests, Personal, Advisory Board, Advice on GU Onc drugs: Surface Oncology; Financial Interests, Personal, Invited Speaker, Best of ESMO20 talk ($1000): UAE Society of Onc; Financial Interests, Personal, Invited Speaker, CME,RCC: WebMed; Financial Interests, Personal, Stocks/Shares, 10,000 options, $0.37/share (2020): Pionyr; Financial Interests, Personal, Stocks/Shares, 100,000 options, $0.16/share (2020): Tempest; Financial Interests, Personal, Invited Speaker, For updating chaptes in GU Oncology: Up-To-Date online textbook; Financial Interests, Institutional, Funding, National co-chair on 3 ongoing trials: ALLIANCE Cooperative Group; Financial Interests, Institutional, Funding, National chair: AstraZeneca; Financial Interests, Institutional, Funding, National chair: BMS; Financial Interests, Institutional, Research Grant, GU oncology translational research through IION program: BMS; Financial Interests, Institutional, Funding, SC member: Eisai; Financial Interests, Institutional, Funding, National co-chair: EMD-Serono; Financial Interests, Institutional, Funding, National chair: Exelixis; Financial Interests, Institutional, Research Grant, fo GU translational research: Exelixis; Financial Interests, Institutional, Principal Investigator, Local PI: GSK; Financial Interests, Institutional, Funding, Chair of trial: Lillly; Financial Interests, Institutional, Funding, National chair: Merck; Financial Interests, Institutional, Funding, National chair: Peloton; Financial Interests, Personal, Funding, National co-chair: Pfizer; Financial Interests, Institutional, Principal Investigator, Local PI: Roche; Financial Interests, Institutional, Research Grant, For Health Outcomes Research: Roche; Financial Interests, Institutional, Principal Investigator, Local PI: Surface Oncology; Financial Interests, Institutional, Funding, National Chair: Takeda; Financial Interests, Institutional, Funding, National Chair: Tracon; Non-Financial Interests, Personal, Leadership Role, Co-Chair of the meeting, 2019, 2020: Kidney Cancer Research Summit of Kidney CAN; Non-Financial Interests, Personal, Principal Investigator, Trial Global and National PI and GU Cancers, mostly Kidney Cancer: Multiple Academic and Industry entities; Non-Financial Interests, Personal, Other, Grants reviewers: AACR; Non-Financial Interests, Personal, Other, Track Leader/Session chair/Speaker/Discussant: ASCO; Non-Financial Interests, Personal, Other, Speaker/Discussant: ESMO; Non-Financial Interests, Institutional, Other, Access to genomic database: Foundation Med; Non-Financial Interests, Institutional, Other, Access to genomic database: Guardant; Non-Financial Interests, Institutional, Other, Access to genomic database: Invitae; Non-Financial Interests, Personal, Other, Medical writing and editorial assistance support (e.g. Clinical Thinking, Envision Pharma Group, Fishawack Group of Companies, Health Interactions, Parexel, Oxford PharmaGenesis, pharmagenesis, and others). However, first draft frequently initiated by myself when I am 1st author: Medical Communication; Non-Financial Interests, Personal, Other, Reviewer of papers: Various Journals (e.g. NEJM, Lancet, JCO). H.J. Hammers: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Corvus; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Principal Investigator, Local PI: BMS; Financial Interests, Institutional, Principal Investigator, Local PI: Merck. E.R. Plimack: Financial Interests, Personal, Advisory Board, Scientific Advisory: BMS; Financial Interests, Personal, Advisory Board, Scientific Advisory: Calithera; Financial Interests, Personal, Advisory Board, Scientific Advisory: Genentech; Financial Interests, Personal, Advisory Board, Scientific Advisory: Janssen; Financial Interests, Personal, Advisory Board, Scientific Advisory: MEI Pharma; Financial Interests, Personal, Advisory Board, Scientific Advisory: Merck; Financial Interests, Personal, Advisory Board, Scientific Advisory: Pfizer; Financial Interests, Personal, Advisory Board, Scientific Advisory: Seattle Genetics; Financial Interests, Personal, Advisory Board, Scientific Advisory: AstraZeneca; Financial Interests, Personal, Advisory Board, Scientific Advisory: Infinity Pharma; Financial Interests, Institutional, Principal Investigator, Coordinating PI, funding for the conduct of clinical trials: Astellas; Financial Interests, Institutional, Principal Investigator, Coordinating PI, funding for the conduct of clinical trials: BMS; Financial Interests, Institutional, Principal Investigator, Coordinating PI, funding for the conduct of clinical trials: Genentech; Financial Interests, Institutional, Principal Investigator, Coordinating PI, funding for the conduct of clinical trials: Merck; Non-Financial Interests, Personal, Member of the Board of Directors, Board of Directors: ASCO. C.G. Porta: Financial Interests, Personal, Invited Speaker, Seminars to Medical Direction Personnel on kidney cancer: Angelini; Financial Interests, Personal, Advisory Board, Consultancy relative to urogenital cancers: AstraZeneca; Financial Interests, Personal, Advisory Board, Advisor relative to development of therapeutics in GU Oncology; speaker at BMS-sponsored meetings; protocol steering committee member: BMS; Financial Interests, Personal, Advisory Board, Advisor role relative to the development of Lenvatinib in RCC and HCC; protocol steering committee member: Eisai; Financial Interests, Personal, Invited Speaker, Expert testimony at AIFA; speaker in EUSA-sponsored meetings; advisorrelative to the development of Tivozanib; protocol steering committee member: EUSA; Financial Interests, Personal, Invited Speaker, Personal, Speaker at GE-sponsored meeting relative to the renal toxicityof CT contrast medium; writing engagement: General Electric; Financial Interests, Personal, Invited Speaker, Speaker at Janssen-sponsored meetings: Janssen; Financial Interests, Personal, Advisory Board, Advisor relative to the development of Avelumab in GU malignancies: Merck; Financial Interests, Personal, Invited Speaker, Speaker at Novartis-sponsored meetings: Novartis; Financial Interests, Personal, Expert Testimony, Expert testimony at EMA; consultant for GU Oncology portfolio; Speakerat Pfizer-sponsored meetings: Pfizer; Financial Interests, Personal, Other, Member of the Steering Committee of ipi/Nivo EAP in Italy: BMS; Financial Interests, Personal, Other, Steering Committee Member of CLEAR study: Eisai; Financial Interests, Personal, Other, Steering Committee member for Tivozanib Italian EAP: EUSA; Financial Interests, Personal, Other, Travel support: Roche; Financial Interests, Personal, Invited Speaker, Speaker at Ipsen-sponsored meeting; advisor relative to the developmentof Cabozantinib in RCC: Ipsen; Financial Interests, Personal, Advisory Board, Advisor relative to the development of Pembrolizumab and Belzutifan in RCC; Speaker at MSD-sponsored meetings: MSD. S. George: Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Personal, Advisory Role: Corvus Pharmaceuticals; Financial Interests, Personal, Advisory Role: Sanofi/Genzyme; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Advisory Role: Seattle Genetics/Astellas; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: QED Therapeutics; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Agensys; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Seattle Genetics/Astellas; Financial Interests, Institutional, Research Grant: Calithera Biosciences; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Corvus Pharmaceuticals; Financial Interests, Institutional, Research Grant: Surface Oncology. T.B. Powles: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Other, Travel Accommodations expenses: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Other, Travel Accommodations expenses: Ipsen; Financial Interests, Personal, Advisory Board: Johnson & Johnson; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other, Travel Accommodations, expenses: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Other, Travel Accommodations, expenses: Pfizer; Financial Interests, Personal, Other, Travel Accommodations, expenses: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Johnson & Johnson; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Merck Serono; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Seattle Genetics. F. Donskov: Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Pfizer. H. Gurney: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Pfizer. C.K. Kollmannsberger: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Janssen. M. Grimm: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZEneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: EUSA; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Member of the Board of Directors: Deutsche Gesellschaft für Urologie; Financial Interests, Personal and Institutional, Principal Investigator, Coordinating PI: BMS; Financial Interests, Institutional, Principal Investigator, Local PI: Intuitive Surgical; Financial Interests, Institutional, Principal Investigator, Local PI: Novartis. Y. Tomita: Financial Interests, Institutional, Research Grant: Ono; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Personal, Speaker’s Bureau: Ono; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Astellas. B.I. Rini: Financial Interests, Personal, Advisory Board: Alkermes; Financial Interests, Personal, Advisory Board: Aravive; Financial Interests, Personal, Advisory Board: Arrowhead; Financial Interests, Personal, Advisory Board: AVEO; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Corvus; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Synthorx; Financial Interests, Personal, Stocks/Shares: PTC Therapeutics; Financial Interests, Institutional, Funding: Aravive; Financial Interests, Institutional, Funding: Arrowhead; Financial Interests, Institutional, Principal Investigator, Local PI: AstraZeneca; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Merck; Financial Interests, Institutional, Other, Steering Committee Member: Pfizer. M.B. McHenry: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. C. Lee: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. B. Escudier: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Aveo; Financial Interests, Personal, Advisory Board: Eisai.