Abstract 1461P
Background
TRCC represent a rare and aggressive subgroup of RCC. While 1L therapy recommendations and clinical prognostication of pts with clear-cell RCC are well-known, data on TRCC clinical behavior are limited. TRCC is reported to be an immune cold tumor and the data surrounding 1L ICT is scarce.
Methods
This is an international, multicenter, retrospective study of adult pts with metastatic TRCC treated with systemic therapies at centers in France, Belgium and in the US. The main objective was to identify prognostic factors associated with 1L therapy and to estimate overall survival (OS).
Results
Fifty-six pts with metastatic TRCC treated at 11 participating centers were evaluable. Median age was 38 years (range 16-62). IMDC risk group was favorable (9/56; 16%), intermediate (38/56; 68%), poor (8/56; 14%) and unknown for 1 patient. Twenty-nine pts (52%) presented with metastatic disease at initial diagnosis; 42 pts (75%) had prior nephrectomy (Nx). 1L therapy included VEGFR tyrosine kinase inhibitors (TKI), ICT combinations (either with TKI or ICT), or other regimens in 32 (57.1%), 18 (32.2%) and 6 pts (10.7%), respectively. With a median follow-up of 27.8 months, 30 pts died from disease progression; median OS was 13.5 months (mo) (95% CI: 3.9-NA) for pts treated with ICT combinations in 1L versus 36.2 mo (95% CI: 27.7-NA) for others (p=0.001). By univariable analysis, ICT combinations in 1L [HR: 3.8; 95% CI (1.6-8.9), p=0.002] and poor risk IMDC group [HR:4.2; 95%CI (1.25-14); p=0.02] were associated with worse OS, while prior Nx was associated with better OS [HR: 0.35; 95% CI (0.16-0.78); p=0.01]. By multivariable analysis, 1L ICT combinations [HR: 3.6; 95% CI (1.4-9.5); p=0.009] and IMDC poor risk group [HR: 4.6; 95%CI (1.05-19.9); p=0.04] were retained as independent variables associated with inferior OS.
Conclusions
These data suggest that some TRCC patients might not derive benefit from a 1L ICT combinations and highlight the variability of this rare subtype of RCC compared to clear-cell RCC. Further collaborative research efforts are needed to elucidate the biology underpinning these findings and to develop more effective therapies for TRCC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
Z. Bakouny: Financial Interests, Institutional, Research Grant: Genetech, Bristol Myers Squibb; Financial Interests, Personal, Writing Engagements: UpToDate. N. Martinez Chanza: Financial Interests, Personal, Advisory Board: Ipsen, Merck, Merck, Astellas; Financial Interests, Personal, Invited Speaker: Janssen. S. Negrier: Financial Interests, Personal and Institutional, Research Grant, and non-financial support: Pfizer, IPSEN; Financial Interests, Personal, Advisory Board, and non-financial support: BMS, MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker, and non-financial support: Eisai. L. Campedel: Financial Interests, Personal, Advisory Board, and travel reimbursement: Pfizer, BMS, MSD, Bayer. D. Borchiellini: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bayer, Bristol Myer Squibb, Ipsen, Janssen, Merck, Pfizer; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Invited Speaker, Clinical Research: Astellas, AstraZeneca, Bayer, Bristol Myer Squibb, Exelixis, Infinity, Janssen, MSD, Roche, Taiho Oncology. Y. Vano: Financial Interests, Personal, Advisory Board: Ipsen, BMS, MSD, Pfizer, Novartis, Merck; Financial Interests, Institutional, Funding, Funding support for the CABIR study: Ipsen; Financial Interests, Institutional, Funding, Funding support for the BIONIKK study: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, Member of the scientific committee of the WITNESS study: Bristol Myers Squibb. P. Barthelemy: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck, Pfizer, Ipsen, Bayer, Janssen Cilag, Astellas, Novartis, AMGEN; Financial Interests, Personal, Invited Speaker: AstraZeneca, Seagen. S.R. Viswanathan: Financial Interests, Personal, Advisory Role: MPM Capital, Vida Ventures; Other, Personal, Other, spouse is an employee of and holds equity in Kojin Therapeutics: Kojin Therapeutics. 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, Invited Speaker, unpaid https://www.accru.org/main/public/index.xhtml: ACCRU; Financial Interests, Personal, Invited Speaker, 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)); 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, 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, 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. L. Albiges: Financial Interests, Institutional, Other, Consulting: Astellas, AstraZeneca, BMS, EISAI, Ipsen, Janssen, MSD, Merck, Novartis, Pfizer; Non-Financial Interests, Principal Investigator: Pfizer, BMS, Ipsen, AVEO, AstraZeneca, MSD; Non-Financial Interests, Other, Clinical trial steering committee: Roche, Exelixis; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Other, Medical Steering Committee: Kidney Cancer Association; Non-Financial Interests, Other, Member of the Renal Cell Carcinoma Guidelines Panel: European Association of Urology (EAU); Non-Financial Interests, Other, Member of the Kidney Cancer Research Summit scientific committee 2021: Kidney Can; Other, Scientific Committee: BMS France. N. Tannir: Financial Interests, Personal and Institutional, Research Grant, and consulting fees and honoraria: BMS; Financial Interests, Institutional, Research Grant: Epizyme, Mirati Therapeutics; Financial Interests, Personal and Institutional, Research Grant, and consulting fees, honoraria and advisory board: Exelixis, Novartis; Financial Interests, Personal, Advisory Role: Argos Therapeutics, Pfizer; Financial Interests, Personal, Advisory Board, and consulting fees and honoraria: Eisai, Nektar Therapeutics, Oncorena. G. Malouf: Financial Interests, Personal, Advisory Role, and travel grant: MSD, BMS, Ipsen; Financial Interests, Personal, Advisory Role: Pfizer. All other authors have declared no conflicts of interest.