Abstract 1464P
Background
The impact of impaired renal function on the efficacy of contemporary 1st line immuno-oncology combination therapies for mRCC in a real world setting is unknown.
Methods
Using the IMDC, a large, multinational, observational cohort study, we identified patients treated with 1L ipilimumab nivolumab (IOIO) or approved PD-1(L1)/vascular endothelial growth factor (IOVE) inhibitor combinations. Baseline characteristics, objective response rate, time to treatment failure and overall survival were captured. Modification of diet in renal disease (MDRD) was used to calculate the estimated glomerular filtration rate (eGFR) at initiation of therapy. IMDC risk group adjusted logistic and Cox regressions were used.
Results
Out of 1059 patients with a documented eGFR, 756 (71.4%) received IOIO and 303 (28.6%) received IOVE. Patients with an eGFR <60 (n=513) were more likely to be older (median 65.1 vs 61.3 yrs p<0.0001) and undergone a nephrectomy (82.4% vs 50.6% p <0.0001) than those with an eGFR ≥60. However, the eGFR <60 group, was less likely to have poorer prognostic features such as bone mets (27.7% vs 38.6% p=0.0002) and poor risk IMDC risk status (22% vs 36% p<0.0001) than the GFR ≥60 group. An eGFR <60 did not have an impact on objective response (OR 0.93 95% CI 0.70 – 1.23 p=0.49), time to next treatment (HR 1.13 95% CI 0.94 – 1.36 p=0.18) or overall survival (HR 1.24 95% CI 0.96 – 1.59 p=0.09). Sensitivity analyses examining eGFRs of <45 (HR 1.23 95% CI 0.91 – 1.67 p=0.18) and <15 (HR 1.32 95% CI 0.33 – 5.35 p=0.69) found consistent results. Modelling eGFR as a continuous variable found that every 1ml/min drop in eGFR lead to a HR of 0.999 (95% CI 0.995 – 1.002 p=0.5073). Table: 1464P
| eGFR ≥ 60 n=546 | eGFR <60 n=513 | P value | |
| Objective Response | 42.30% | 43.20% | 0.77 |
| Median Time to Next Treatment | 16.3 months (95% CI 13.4 - 22.8) | 18.4 months (95% CI 15.4 - 22.5) | 0.68 |
| Median Overall Survival | 53.5 months (95% CI 41.4 - NE) | 44.4 months (95% CI 36.5 - 53.5) | 0.72 |
Conclusions
Baseline renal function does not adversely impact the effectiveness of 1L immuno-oncology combination therapies in mRCC. Clinicians should not restrict access to these therapies based on renal function.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Interna.
Disclosure
S.K. Pal: Financial Interests, Personal, Advisory Role: Novartis, Astellas, Medivation, Pfizer, Aveo, Myriad, Genentech, Exelixis, BMS. T.B. Powles: Financial Interests, Personal and Institutional, Advisory Board: Seagen, Pfizer, Novartis, Merck, Janssen, Ipsen, Incyte, Roche, Exelixis, EMD Serono, Eisai, BMS, AstraZeneca, Astellas. C.K. Kollmannsberger: Financial Interests, Personal, Advisory Board: Astellas, Bayer, BMS, Eisai, Ipsen, Janssen, Merck, Pfizer. B. Beuselinck: Financial Interests, Institutional, Advisory Board, Advisory board: BMS, MSD; Financial Interests, Institutional, Expert Testimony, Testimony: BMS; Financial Interests, Institutional, Invited Speaker, Conference: Merck. N. Agarwal: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bayer, BMS, Clovis Oncology, Eisai, Eli Lilly, EMD Serono, Foundation Medicine, Genentech, Janssen, Merck, Nektar Therapeutics, Novartis, Pfizer, Pharmacyclics, Seagen. 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, Unpaid https://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. D.Y.C. Heng: Financial Interests, Personal, Advisory Board: Pfizer, Merck, BMS, Ipsen, Novartis, AstraZeneca, Roche; Financial Interests, Personal, Invited Speaker: Exilexis; Financial Interests, Institutional, Invited Speaker: BMS, Pfizer, Ipsen. All other authors have declared no conflicts of interest.