1893P Immune-related adverse events from contemporary first-line combination therapies in metastatic renal cell carcinoma: Results from the IMDC.

Abstract

Background: A favourable relationship between immune related adverse events (irAEs) and survival has been established across tumours. However, for patients with metastatic renal cell carcinoma (mRCC) treated with Immuno-oncology (IO) based combination first-line therapies, the prognostic impact of irAEs remains uncertain. Method(s): To examine the association between irAEs and survival among first-line ipilimumab-nivolumab (IOIO) or anti-PD-1/PD-L1 + vascular endothelial growth factor receptor inhibitors (IOVE), we used an IMDC dataset, a large multicenter international cohort study. Only clinically impactful irAEs (requiring systemic steroids or IO treatment delay), were included. To minimize immortal time bias, only patients surviving longer than 3 months were included in the survival analysis. Result(s): 328/1448 (22.7%) patients developed an irAE. As per table, patients that developed an irAE had a similar median age and BMI, were more likely to have pre-existing auto-immune co-morbidities, improved IMDC risk and clear cell histology. Frequency of irAEs were similar in patients treated with IOIO and IOVE (23.2% vs 21.2% respectively p=0.40). Cytoreductive nephrectomy (OR 1.69 95% CI 1.16 - 2.47 p=0.006) and non-sarcomatoid histology (OR 1.98 95% CI 1.26 - 3.12 p=0.003) were more likely to be associated with an increased odds of developing irAEs. Development of an irAE was associated with a longer overall survival, median not estimable [95% CI 44.5 - not estimable] vs 47.2 months [95% CI 40.7 - 53.4] logrank p = 0.005). A favourable independent association of irAEs with overall survival was found in multivariable analysis, after IMDC risk factor adjustment (HR 0.68 [95% CI 0.52 - 0.89] p=0.006). [Formula presented] Conclusion(s): Development of an irAE is a potential treatment biomarker of improved outcome for patients treated with first-line IO combination therapy in mRCC. Patients with pre-existing auto-immune co-morbidities at baseline have a high incidence of irAEs. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: 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. C.K. Kollmannsberger: Financial Interests, Personal, Advisory Board, ad-hoc advisory board: Pfizer, Ipsen, BMS, Eisai, Merck, Bayer, Astellas; Financial Interests, Personal, Invited Speaker, honoraria for educational presentation: Pfizer; Financial Interests, Personal, Invited Speaker, honoraria for educational lectures: Ipsen; Financial Interests, Personal, Invited Speaker, honoraria for presentations: BMS, Eisai, Merck, Seagen, Bayer, Astellas, Janssen; Financial Interests, Personal, Advisory Board, Ad-hoc advisory board: Seagen, Janssen, AstraZeneca. S. North: Financial Interests, Personal, Advisory Board, honoraria: Astellas, BMS, Janssen, Merck, Roche, Sanofi, Bayer, AstraZeneca; Financial Interests, Institutional, Local PI, per case funding: Sanofi, AstraZeneca, Ipsen, Astellas. 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. A. Lalani: Financial Interests, Personal, Other, Ad hoc consultation: AbbVie, Astellas, BMS, Eisai, Ipsen, Janssen, Merck, Pfizer, McKesson, AstraZeneca, EMD Serono; Financial Interests, Institutional, Research Grant: BMS, BioCanRx, EMD Serono, Ipsen, Novartis, Roche. 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, (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, Takeda, Exelixis, AstraZeneca, Tracon, Peloton; Financial Interests, Institutional, Local PI: 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, Local PI, 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, 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 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 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. All other authors have declared no conflicts of interest.Copyright © 2023 European Society for Medical Oncology