Association between baseline radiological tumor burden (BRTB) and outcomes in metastatic clear cell renal cell carcinoma (mccRCC) treated with first line (1L) immunotherapy (IO)-based regimens

BackgroundBRTB has been associated with clinical outcomes in patients (pts) treated with IO in solid tumors. However, its prognostic value for patients with mRCC remains unclear. Herein, we evaluate the utility of BRTB as prognostic factor in pts with mccRCC treated with 1L IO-based regimens.MethodsWe reviewed data from 150 pts with mccRCC treated at Dana-Farber Cancer Institute from August 2014 to October 2023, who received ≥ 1 dose of an IO-based regimen and with CT-scan reports within 1 month prior to 1L initiation. BRTB was assessed by a single operator per RECIST v1.1. The primary outcome was overall survival (OS). Secondary outcomes included time to treatment failure (TTF) and time to next therapy (TTNT). Multivariable Cox regression models included IMDC risk groups, previous nephrectomy, and presence of bone, liver, or brain metastases prior to 1L initiation.ResultsOverall, 9% (13/150) had favorable risk, 51% (77/150) had intermediate risk, and 20% (30/150) had poor risk by IMDC. Nephrectomy prior to the start of 1L therapy was performed in 73% (109/150) of pts. Brain, bone, or liver metastases were observed in 41% (61/150) of pts. The 4-year OS estimates are included in the table. On univariate analysis, every 1 cm increase in BRTB was associated with a 5% increased risk of death (HR: 1.05; 95% CI: 1.03–1.08; p<0.0001). On multivariable analysis, BRTB remained significantly associated with OS (HRadjusted: 1.04; 95% CI: 1.00–1.08; p=0.03). However, BRTB was not significantly associated with TTF (HRadjusted: 0.99; 95% CI: 0.97–1.01; p=0.428) or TTNT (HRadjusted: 1.01; 95% CI: 0.99–1.03; p=0.453).ConclusionsBRTB is an independent prognostic factor for OS in pts with mccRCC treated with 1L IO-based regimens. Validation of these findings in a large clinical trial cohort is underway. Table: 1705P 4-year overall survival estimates based on tertiles of BRTB Tertiles 4 - year OS estimates (95% CI) Log-rank P-value 1st tertile (0 – 7.5 cm) 84% (74 – 97) P < 0.0001 2nd tertile (7.6 – 15.3 cm) 60% (45 – 81) 3rd tertile (15.4 – 47.7 cm) 43% (29 – 66) OS: Overall Survival; CI: Confidence Interval Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureD. Vasseur: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche. S. Baca: Financial Interests, Personal, Ownership Interest: Precede Biosciences. D.A. Braun: Financial Interests, Personal, Invited Speaker, Speaker on innovation in oncology and clinical trial design: LM Education/Exchange Services; Financial Interests, Personal, Other, Consulting: Octane Global, Defined Health, Adept Field Solutions, Slingshot Insights, Blueprint Partnerships, Charles River Associates, Trinity Group, Insight Strategy, Catenion, PWW Consulting, Haymarket; Financial Interests, Personal, Advisory Board, Advisory Board: Exelixis, Aveo; Financial Interests, Personal, Invited Speaker: Aptitude Health, AbbVie, ASCO Post RCC Roundtable, Targeted Oncology, Pfizer, Medscape; Financial Interests, Personal, Other, Advisor: Fortress Biotech (subsidiary), DLA Piper; Financial Interests, Personal, Other, Co-Founder: CurIOS; Financial Interests, Personal, Advisory Board: Elephas Bio, Merck, Eisai, Compugen, Link Cell Therapies, Scholar Rock, Neomorph; Financial Interests, Personal, Other, Medical education: Accolade 2nd.MD; Financial Interests, Personal, Other, stock options: Elephas; Financial Interests, Personal, Research Grant: AstraZeneca, Exelixis; Non-Financial Interests, Advisory Role: Bristol Myers Squibb; Non-Financial Interests, Member: ASCO. W. Xie: Financial Interests, Personal, Other, Consulting: Convergent Therapeutics, Inc. 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, Advisory Board, GU cancer drug development: alkermes, Gilead; Financial Interests, Personal, Other, Study section reviewer. $200.00 per day for 1 day: National Cancer Institute; Financial Interests, Personal, Other, Cancer Center Grand Rounds: Cleveland Clinic; Financial Interests, Personal, Advisory Board, Advisory Board/month: CURESPONSE; Financial Interests, Personal, Advisory Board: Tempest, Precede Bio (not publicly traded)); 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, advisor: Pionyr (not publicly traded), Tempest (publicly traded), Osel (not publicly traded), Precede Bio (not publicly traded)), CURESPONSE (not publicly traded), Inndura; Financial Interests, Personal, Stocks/Shares: Primium; 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; Financial Interests, Institutional, Local PI, National Chair: Roche; Financial Interests, Institutional, Funding, National co-chair: Pfizer, EMD-Serono; Financial Interests, Institutional, Funding, Chair of trial: Lilly; Financial Interests, Institutional, Local PI: Surface Oncology, GSK; 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, Local PI, leads trials as PI: Nikang; Non-Financial Interests, Leadership Role, Co-Chair of the meeting, 2019- current and BOD member (unpaid): 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, 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, Member: ASCO, AACR; 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, 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, Professor at HMS, Please see https://hms.harvard.edu/ for mission statement (non-profit school): Harvard Medical School (HMS); Other, The institution filed patents related to biomarkers of immune checkpoint blockers, and circulating tumor DNA. No money made and some patents were abandoned: Filed patents. All other authors have declared no conflicts of interest.