Abstract 1903P
Background
L+P is a standard of care (SoC) in 1L RCC based on significantly improved efficacy versus S in the CLEAR study [ Motzer 2021 ]. We report tumor response by baseline metastases at the final prespecified overall survival analysis timepoint (cutoff date: 31 Jul 22).
Methods
Treatment-naive adults with RCC were randomized to L (20 mg orally QD in 21-day cycles) plus P (200 mg IV Q3W) or L (18 mg orally QD in 21-day cycles) plus everolimus (5 mg orally QD in 21-day cycles) or S (50 mg orally QD; 4 wks on/2 wks off). This post hoc analysis examined response by baseline metastases in L+P (n=355) vs S (n=357) arms. Objective response rate (ORR), complete response (CR) rate, partial response (PR) rate, and progression-free survival (PFS) via independent imaging review (IIR) per RECIST v1.1 by baseline metastatic characteristics (site of metastasis [lung, lymph node, bone, liver, brain], number of metastatic sites [1 vs ≥2] and sums of diameters of target lesions [≥60 mm vs <60 mm]) are analyzed. Odds ratios (ORs) for ORR and hazard ratios (HRs) for PFS with 95% CIs are reported.
Results
The most common metastatic site by IIR at baseline was lung (L+P: 71.0%; S: 63.9%); 22.5% and 24.9% of pts, respectively, had bone metastases. 65.1% Of pts randomized to L+P and 66.1% of pts randomized to S had metastases at ≥2 sites. ORR favored L+P irrespective of metastatic site (Table). ORR favored L+P in pts with 1 (OR, 2.98 [95% CI 1.71, 5.21]) or ≥2 metastatic sites (OR, 5.06 [95% CI 3.40, 7.53]), and in pts with target lesion diameter sums ≥60 mm (OR, 10.50 [95% CI 6.08, 18.13]) or <60 mm (OR 3.14 [95% CI 1.94, 5.07]). PFS favored L+P vs S across subgroups (Table). CR and PR rates were higher in L+P vs S across subgroups (to be reported).
Conclusions
Tumor response favored L+P in all subgroups of interest, particularly in patients with increased burden of disease. Data further support L+P as a SoC in pts with 1L RCC.
Table: 1903P
L+P vs S | ||
ORRa,b OR (95% CI) | PFSa,b HR (95% CI) | |
Metastatic Site a | ||
Lung | ||
Y | 5.19 (3.48, 7.72) | 0.41 (0.32, 0.52) |
N | 3.02 (1.75, 5.20) | 0.51 (0.34, 0.75) |
Lymph Node | ||
Y | 3.66 (2.28, 5.88) | 0.49 (0.37, 0.66) |
N | 4.83 (3.14, 7.43) | 0.45 (0.34, 0.60) |
Bone | ||
Y | 4.09 (2.11, 7.94) | 0.50 (0.33, 0.77) |
N | 4.30 (2.97, 6.20) | 0.45 (0.36, 0.57) |
Liver | ||
Y | 3.51 (1.68, 7.30) | 0.48 (0.31, 0.77) |
N | 4.53 (3.17, 6.47) | 0.46 (0.36, 0.57) |
Brain | ||
Yc | 3.00 (0.43, 20.72) | 0.32 (0.07, 1.59) |
N | 4.29 (3.11, 5.92) | 0.47 (0.38, 0.57) |
No. Metastatic Sites a | ||
1 | 2.98 (1.71, 5.21) | 0.60 (0.41, 0.87) |
≥2 | 5.06 (3.40, 7.53) | 0.40 (0.31, 0.50) |
Target Lesion Diameter Sums a | ||
≥60 mm | 10.50 (6.08, 18.13) | 0.39 (0.29, 0.53) |
<60 mm | 3.14 (1.94, 5.07) | 0.53 (0.40, 0.71) |
aIIR; bRECIST v1.1; cL+P n=6; S n=10.
Clinical trial identification
NCT02811861.
Editorial acknowledgement
Medical writing support was provided by Irene Minkina, PhD, of Oxford PharmaGenesis Inc., Newtown, PA, USA, with funding by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Legal entity responsible for the study
Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Funding
This study was sponsored by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
V. Gruenwald: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Eisai, Ipsen, Janssen Cilag, Merck Serono, MSD, Pfizer, Roche, Novartis, Astellas; Financial Interests, Personal, Advisory Board: BMS, Eisai, Merck Serono, MSD, Nanobiotix, Pfizer, Roche, Apogepha, EUSA Pharm, Debiopharm, Oncorena, PCI Biotech; Financial Interests, Personal, Stocks/Shares: BMS, MSD, AstraZeneca, Seattle Genetics; Financial Interests, Institutional, Invited Speaker: BMS, Novartis; Financial Interests, Institutional, Research Grant: Ipsen, MSD, Pfizer, BMS; Financial Interests, Personal and Institutional, Invited Speaker: Eisai, Ipsen; Financial Interests, Invited Speaker: PharmaMar; Non-Financial Interests, Member: ASCO, German medical Oncology and Hematology Society; Non-Financial Interests, Advisory Role: German Cancer Society; Non-Financial Interests, Leadership Role: Working Group medical oncology; Other, Other, Travel support to ESMO 2022 : Pfizer; Other, Other, Travel support for meeting: Merck Serono. R.R. McKay: Financial Interests, Personal, Advisory Board: AstraZeneca, Aveo, Bayer, BMS, Calithera, Dendreon, Exelixis, JNJ, Lilly, Merck, Pfizer, Sanofi, SeaGen, Sorrento Therapeutics, Telix, Tempus; Financial Interests, Personal, Other, Molecular tumor board: Caris; Financial Interests, Personal, Other, Consultant: Dendreon, Myovant; Financial Interests, Personal, Invited Speaker: Exelixis, Merck, Novartis, Pfizer; Non-Financial Interests, Trial Chair: AstraZeneca, Bayer; Non-Financial Interests, Steering Committee Member: Aveo, Eli Lilly, Merck; Non-Financial Interests, Local PI: BMS, Calibr, Eli Lilly, Genentech, JNJ, Merck, Oncternal, Poseida, Scholar Rock, SeaGen, Xencor; Non-Financial Interests, Institutional, Local PI: Exelixis. T. Buchler: Financial Interests, Personal, Invited Speaker: Roche, BMS, Astellas, Janssen, Ipsen, Merck; Financial Interests, Personal, Advisory Board: Bayer, BMS, Ipsen, Merck, Servier, Eli Lilly, Pfizer, Accord; Financial Interests, Institutional, Invited Speaker: BMS, Merck, Bayer, Exelixis, Eisai, Eli Lilly, Roche, MSD; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Advisory Role: Leram Pharmaceuticals. M. Eto: Financial Interests, Personal, Speaker’s Bureau: MSD, Ono, Takeda, Merck, AstraZeneca, Eisai, BMS, Astellas, Pfizer, Janssen; Financial Interests, Personal, Advisory Board: Eisai, Merck, BMS, Chugai Pharmaceutical, Pfizer, AstraZeneca, Takeda, MSD; Financial Interests, Personal, Research Grant: Sanofi, Ono, Takeda. T. Takagi: Financial Interests, Institutional, Invited Speaker: Eisai. D. Keizman: Financial Interests, Personal, Invited Speaker: MSD, BMS, Pfizer, Astellas; Financial Interests, Personal, Advisory Board: MSD, BMS, Pfizer, Astellas, Eisai. C. Suarez Rodriguez: Financial Interests, Personal, Advisory Board: Astellas Pharma, Bayer, BMS (Inst), Ipsen, Pfizer S.L.U, Sanofi- Aventis, Hoffmann-La Roche LTD, Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker: Astellas Pharma, BMS (Inst), Ipsen, Pfizer S.L.U, Hoffmann-La Roche LTD, Merck; Financial Interests, Institutional, Funding: Ipsen. S. Negrier: Financial Interests, Personal, Advisory Board: Pfizer, BMS, Ipsen, MSD, Eisai; Financial Interests, Institutional, Research Grant: Pfizer, Ipsen; Other, Other, Reimbursement of travel costs + Congress registration: Pfizer, Ipsen, MSD; Other, Other, Reimbursement of travel costs: BMS, Eisai. J. Lee: Financial Interests, Personal, Advisory Board: BMS, Astellas Korea, AstraZeneca, MSD, Merck; Financial Interests, Personal, Stocks/Shares: Merck, Johnson and Johnson, Amgen, Black Diamond Therapeutics, Zymeworks, Karyopharm Therapeutics; Financial Interests, Institutional, Invited Speaker: Pfizer, Janssen, Novartis, BMS, Genentech, Roche, AstraZeneca, MSD, Merck, Bayer Shering Pharma, Seagen, GI Innovation, Amgen, Oscotec. J. Bedke: Financial Interests, Personal, Advisory Board: AstraZeneca, Astellas, Eisai; Financial Interests, Personal, Advisory Board, Advisory Board and Speakerś Bureau: BMS, Ipsen, MSD, Merck Sorono, Pfizer, Roche, Janssen; Financial Interests, Institutional, Advisory Board: BMS, Pfizer; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Astellas, BMS, BMS, Eisai, MSD, MSD, Ipsen, Novartis, Nektar, Pfizer, Pfizer, Roche, Seagen, Seagen; Other, Other, Member of the Renal Cell Carcinoma Guidelines Panel: European Association of Urology. M. Staehler: Financial Interests, Personal, Other, Consultant and honoraria: Pfizer, GSK, Novartis, Bayer, Aveo, EUSAPharm, Astellas, Ipsen, Exelixis, Pelloton, Eisai, BMS, MSD, Apogepha; Financial Interests, Personal, Other, Consultant: Roche, Oncorena, Janssen; Financial Interests, Institutional, Research Grant: Pfizer, GSK, Aveo, BMS, Novartis, Bayer, Roche/Genentech, Immatics, Wilex, Ipsen, Exelixis, Eisai. C.K. Kollmannsberger: Financial Interests, Personal, Invited Speaker: Pfizer, Ipsen, BMS, Merck, Eisai, Astellas, Bayer, Janssen, Seagen; Financial Interests, Personal, Advisory Board: Pfizer, Ipsen, BMS, Merck, Eisai, Astellas, Bayer, Janssen, Seagen; Non-Financial Interests, Institutional, Principal Investigator: BMS, Ipsen, Eisai; Non-Financial Interests, Institutional, Advisory Board: Merck. T.K. Choueiri: Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: BMS, Pfizer, Merck, Exelixis, AstraZeneca; Financial Interests, Personal, Advisory Board, Advice on Onc drugs: Lilly, EMD Serono, Infinity; Financial Interests, Personal, Advisory Board, Advice on RCC drug: Calithera; Financial Interests, Personal, Invited Speaker, RCC drug: Ipsen; Financial Interests, Personal, Advisory Board, Advice on GU Onc drugs: Surface Oncology; Financial Interests, Personal, Other, Consultant on onc drugs: Analysis Group; Financial Interests, Personal, Invited Speaker, CME, ww2.peerview.com: Peerview; Financial Interests, Personal, Invited Speaker, CME, gotoper.com: PER; Financial Interests, Personal, Invited Speaker, CME, researchtopractice.com: ResearchToPractice; Financial Interests, Personal, Invited Speaker, National Association of Managed Care: NAMC; Financial Interests, Personal, Invited Speaker, ASCO-related event: ASCO-SITC; Financial Interests, Personal, Other, Grant review to Orien Network ($400): ORIEN; Financial Interests, Personal, Advisory Board, Advising oncology strategy: Aptitude Health; Financial Interests, Personal, Invited Speaker, Best of ASCO19 talk: Advent health; Financial Interests, Personal, Invited Speaker, Best of ESMO20 talk ($1000): UAE Society of Onc; Financial Interests, Personal, Invited Speaker, CME, mjhlifesciences.com (OncLive): MJH life sciences; Financial Interests, Personal, Invited Speaker, Grand Rounds: MDACC; Financial Interests, Personal, Invited Speaker, RCC webinar: Cancernet; Financial Interests, Personal, Invited Speaker, CME, Kidney Cancer Association ($1300): France Foundation; Financial Interests, Personal, Invited Speaker, CME, RCC: Springer, WebMed; Financial Interests, Personal, Invited Speaker, CME, ImmunoOncology in RCC: ASiM, CE; Financial Interests, Personal, Invited Speaker, CME, PodCast in RCC ($500.00): Caribou Publishing; Financial Interests, Personal, Invited Speaker, Reimbursement ($432.00): Kidney Cancer Association; Financial Interests, Personal, Other, member of the DSMB for clinical trial: Aravive; Financial Interests, Personal, Other, on the DMC of clinical trial: Aravive; Financial Interests, Personal, Advisory Board, GU cancer drug development: alkermes, Gilead; Financial Interests, Personal, Member of Board of Directors, unpaidhttps://www.accru.org/main/public/index.xhtml: ACCRU; Financial Interests, Personal, Member of Board of Directors, Unpaidhttps://kidneycan.org: KidneyCan; Financial Interests, Personal, Other, External Advisory Board Member: Gustave Roussy; Financial Interests, Personal, Stocks/Shares: Pionyr (not publicly traded), Tempest (publicly traded), Osel (not publicly traded), Nuscan ((not publicly traded)), CURESPONSE; Financial Interests, Personal, Royalties, For writing and updating chapters in GU Oncology: Up-To-Date online textbook; Financial Interests, Institutional, Funding, National Chair: BMS, Merck, Exelixis, AstraZeneca, Takeda, Tracon, Peloton; Financial Interests, Institutional, Invited Speaker: Roche, Surface Oncology, GSK; Financial Interests, Institutional, Funding, National co-chair: Pfizer, EMD-Serono; Financial Interests, Institutional, Funding, Chair of trial: Lilly; Financial Interests, Institutional, Funding, SC member: Eisai; Financial Interests, Institutional, Funding, National co-chair on 3 ongoing trials: ALLIANCE Cooperative Group; Financial Interests, Institutional, Research Grant, for GU oncology translational research through IION program: BMS; Financial Interests, Institutional, Research Grant, for GU oncology translational research: Exelixis; Financial Interests, Institutional, Research Grant, For Health outcomes research: Roche; Financial Interests, Institutional, Invited Speaker, leads trials as PI: Nikang; Non-Financial Interests, Leadership Role, Co-Chair of the meeting, 2019-: Kidney Cancer Research Summit of KidneyCAN; Non-Financial Interests, Principal Investigator, Trial Global and National PI with GU Cancers, mostly Kidney Cancer: Multiple Academic and Industry entities; Non-Financial Interests, Personal, Other, Track Leader/Session chair/Speaker/Discussant: ASCO; Non-Financial Interests, Personal, Other, Speaker/Discussant/Track Leader: ESMO; Non-Financial Interests, Institutional, Other, Access to genomic database: Foundation Med, Guardant, Invitae; Non-Financial Interests, Member: ASCO, AACR; Non-Financial Interests, Personal, Other, Grants reviewers: AACR; Non-Financial Interests, Personal, Other, Reviewer of papers: Various journals (e.g. NEJM, Lancet, JCO); Non-Financial Interests, Personal, Other, Medical writing and editorial assistance support (e.g. ClinicalThinking, 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, Other, Political vote usually as “independent”, not a member of any political party. I am an issue voter: General US Politics; Other, Other, Employee at DFCI. Please see https://www.dana-farber.org/ for mission statement (non-profit hospital). I am also the past President of Medical Staff at DFCI 2015-2018: Dana-Farber Cancer Institute (DFCI); Other, Other, Professor at HMS, please see https://hms.harvard.edu/ for mission statement (non-profit school): Harvard Medical School (HMS); Other, Other, No financial interest. Institutional.Filed patents related to biomarkers of immune checkpoint blockers and circulating free methylated DNA. No money made and some patents were abandoned: Filed patents. R.J. Motzer: Financial Interests, Institutional, Research Funding: BMS, Eisai, Exelixis, Genentech/Roche, Merck, Pfizer, Aveo Pharmaceuticals; Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Aveo Pharmaceuticals, Eisai, EMD Serono, Exelixis, Genentech/Roche, Incyte, Lilly, Merck, Novartis, Pfizer, Takeda. J. Burgents: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. C.E. Okpara: Financial Interests, Personal, Full or part-time Employment: Eisai. T.B. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Exelixis, Incyte, Ipsen, Merck, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche, Pfizer, MSD, AstraZeneca, Ipsen; Financial Interests, Personal, Other, Sponsorship for Uromigos Podcast: Mashup Ltd; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, BMS, Exelixis, Ipsen, Merck, MSD, Seattle Genetics, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai. All other authors have declared no conflicts of interest.
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