Abstract 668P
Background
The landscape for first-line (1L) aRCC is rapidly evolving, with P+A and N+C recommended as standard of care irrespective of risk group by the European Association of Urology and the European Society for Medical Oncology. P+A and N+C have similar modes of action and demonstrated a significant efficacy benefit versus sunitinib (S), although no head-to-head data exist. As aRCC significantly impacts HRQoL, understanding HRQoL benefits of these 2 treatments is of interest to inform clinical decision making.
Methods
An anchored MAIC was conducted using patient-level data from the CheckMate 9ER trial (NCT03141177; N+C vs S) and aggregate published data from the KEYNOTE-426 trial (NCT02853331; P+A vs S). Outcomes included Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index – Disease Related Symptoms (FKSI-DRS) and EQ-5D visual analog scale (EQ VAS) due to limited published HRQoL data from KEYNOTE-426. Hazard ratios for time to first and confirmed deteriorations (TTFD and TTCD, respectively) and baseline to week 30 least squares mean differences in these outcomes were re-estimated for CheckMate 9ER using a weighted population and indirectly compared with those in KEYNOTE-426 via a Bayesian framework.
Results
A total of 651 CheckMate 9ER patients (pts) were matched to 861 KEYNOTE-426 pts using age, region, risk group, sites of metastatic disease, and prior nephrectomy. Results from the MAIC favored N+C versus P+A in all outcomes with statistically significant differences for FKSI-DRS and TTFD in EQ VAS score (Table). Table: 668P
| Outcome | MAIC results, N+C vs P+A |
| TTFD, HR (95% CrI) | |
| EQ-5D VAS | 0.73 (0.55–0.96)a |
| TTCD, HR (95% CrI) | |
| EQ-5D VAS | 0.72 (0.52–1.01) |
| FKSI-DRS | 0.48 (0.33–0.69)a |
| Change from baseline at week 30, LSMD (95% CrI) | |
| EQ-5D VAS | 2.55 (–0.88 to 5.98) |
| FKSI-DRS | 1.85 (0.96–2.74)b |
aThe 95% CrI does not contain 1. HR < 1 favors N+C over P+A. bThe 95% CrI does not contain 0. LSMD > 0 favors N+C over P+A. CrI, credible interval; HR, hazard ratio; LSMD, least squares mean difference.
Conclusions
In pts with 1L aRCC, MAIC analyses indicate that compared with P+A, N+C demonstrated a significant improvement in DRS and significantly delayed deterioration in HRQoL. These results, combined with the efficacy and favorable safety profile of N+C, may further inform treatment decisions of clinicians and pts with 1L aRCC.
Clinical trial identification
NCT03141177; NCT02853331.
Editorial acknowledgement
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
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: Bristol Myers Squibb; 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; advisor relative to the development of Tivozanib; protocol steering committee member: EUSA; Financial Interests, Personal, Invited Speaker, Speaker at GE-sponsored meeting relative to the renal toxicity of CT contrast medium; writing engagement: General Electric; Financial Interests, Personal, Invited Speaker, Speaker at Ipsen-sponsored meeting; advisor relative to the development of Cabozantinib in RCC: Ipsen; 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, Advisory Board, Advisor relative to the development of Pembrolizumab and Belzutifan in RCC; Speaker at MSD-sponsored meetings: MSD; 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; Speaker at Pfizer-sponsored meetings: Pfizer; Financial Interests, Personal, Invited Speaker, Member of the Steering Committee of ipi/Nivo EAP in Italy: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, Steering Committee Member of CLEAR study: Eisai; Financial Interests, Personal, Invited Speaker, Steering Committee member for Tivozanib Italian EAP: EUSA; Other, Other, Travel support: Roche. R. Motzer: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Aveo Pharmaceuticals; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Exelixis; 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: Merck; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Principal Investigator, Coordinating PI, funding for trial conduct from sponsorto my employer MSKCC: BMS; Financial Interests, Institutional, Principal Investigator, Coordinating PI, funding for trial conduct from sponsorto my employer MSKCC: Eisai; Financial Interests, Institutional, Principal Investigator, Coordinating PI, funding for trial conduct from sponsorto my employer MSKCC: Exelixis; Financial Interests, Institutional, Principal Investigator, Coordinating PI, funding for trial conduct from sponsorto my employer MSKCC: Genentech/Roche; Financial Interests, Institutional, Principal Investigator, Coordinating PI, funding for trial conduct from sponsorto my employer MSKCC: Merck; Financial Interests, Institutional, Principal Investigator, Coordinating PI, funding for trial conduct from sponsorto my employer MSKCC: Pfizer. F. Ejzykowicz: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. S.I. Blum: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS; Financial Interests, Personal, Stocks/Shares: GlaxoSmithKline. M. Hamilton: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. J.R. May: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. S. Huo: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. P. Kral: Financial Interests, Institutional, Full or part-time Employment, Employee of IQVIA who was contracted to perform the analyses for abstract submission: IQVIA. C. Ivanescu: Financial Interests, Institutional, Full or part-time Employment, Employee of IQVIA who was contracted to perform the the analyses: IQVIA. 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 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 (OncLive): MJH Life Sciences; Financial Interests, Personal, Invited Speaker, National Association of Managed Care: NAMC; Financial Interests, Personal, Other, Grant review to Orien Network ($400): ORIEN; Financial Interests, Personal, Invited Speaker, CME, ww2.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, Royalties, For writing and updating chapters in GU Oncology: Up-To_Date; 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, for 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, for GU oncology translational research: Exelixis; Financial Interests, Institutional, Principal Investigator, Local PI: GSK; Financial Interests, Institutional, Funding, Chair of trial: Lilly; Financial Interests, Institutional, Funding, National Chair: Merck; Financial Interests, Institutional, Funding, National Chair: Peloton; Financial Interests, Institutional, 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, rial Global and National PI with 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, 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, Invited Speaker: Medical Communication; Non-Financial Interests, Personal, Other, Reviewer of papers: Various journals (e.g. NEJM, Lancet, JCO); Non-Financial Interests, Personal, Other, Speaker/Discussant: ESMO. D. Cella: Financial Interests, Personal, Other, Consultant: BMS; Financial Interests, Personal, Other, Consultant: Merck; Financial Interests, Personal, Other, Consultant: Novartis; Financial Interests, Personal, Other, Consultant: Pfizer; Financial Interests, Personal, Officer, President: FACIT.org; Financial Interests, Personal, Licensing Fees: FACIT.org; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer.