1902P - Comparison of cabozantinib (CABO) versus sunitinib (SUN) following first-line (1L) nivolumab plus ipilimumab (NIVO+IPI) for metastatic renal cell carcinoma (mRCC): A target trial emulation using real-world data from the International mRCC Database Consortium (IMDC)

Background

While the benefit of CABO in mRCC is well established post-tyrosine kinase inhibitor, its comparative effectiveness vs SUN after 1L NIVO+IPI is uncertain.

Methods

A target trial emulation was designed using data from the IMDC to estimate the effect of second-line (2L) CABO versus SUN within one year of discontinuing 1L NIVO+IPI on overall survival (OS). Patients (pts) diagnosed after January 1, 2017, were followed from initiation of 2L until death or last known contact. Inverse-probability of treatment weighting was used to adjust for hemoglobin, calcium, platelets, and neutrophils at 2L, Karnofsky performance score (KPS) at 2L, time from diagnosis to initiation of 2L, and response to 1L NIVO+IPI. Treatments were compared using adjusted Kaplan-Meier curves and adjusted hazard ratios (HR) from a Cox regression model. Missing data were addressed with multiple imputation by chained equations. E-values were used to assess the likelihood findings could be explained by residual confounding.

Results

121 and 123 pts who received CABO and SUN after 1L NIVO+IPI were included. Among the baseline characteristics, only the proportion with a KPS < 80% differed significantly between CABO (21%) and SUN (45%) (p = 0.002) (Table). The objective response was 27% (21/79) for CABO vs 20% (18/89) for SUN with a median time to treatment failure of 8.5 (95% CI: 6.9-12.9) and 4.5 (95% CI 3.7-5.8) months. Median OS was 21.4 (95% CI 17.9–NA) months from initiation of CABO and 10.1 (95% CI 7.6–17.7) months for SUN (Adjusted HR 0.44 (95% CI: 0.23-0.85)). This corresponds to an E-value of 2.91 suggesting a low likelihood of findings being due to residual confounding alone.

Conclusions

This investigation provides real-world evidence supporting CABO as a 2L treatment option for mRCC following NIVO+ IPI . Table: 1902P

Characteristics of pts receiving 2L CABO and SUN

LLN, lower limit of normal; SD, standard deviation; ULN, upper limit of normal. *: At 2L.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors, IMDC and Ipsen Biopharmaceuticals Canada Inc.

Funding

Ipsen Biopharmaceuticals Canada Inc.

Disclosure

B.A. McGregor: Financial Interests, Personal, Advisory Board: Exelixis, BMS, Dendreon, SeaGen, Astellas, Eisai, Pfizer; Financial Interests, Personal, Invited Speaker: EMD Serono, SeaGen; Financial Interests, Institutional, Trial Chair: Pfizer, Exelixis, Exelixis, BMS, Gilead; Financial Interests, Institutional, Local PI: Calithera, SeaGen, Aveo; Non-Financial Interests, Member: ASCO. N.S. Basappa: Financial Interests, Personal, Advisory Board: Ipsen, Eisai, Pfizer, AstraZeneca, Janssen Inc, EMD Serono, Astellas, Bayer, BMS, Seagen, Takeda; Financial Interests, Institutional, Research Grant, Research Grant: Ipsen; Other, Other, Travel grant/support: Ipsen; Other, Other, Travel Grant/support: Eisai. S.K. Pal: Financial Interests, Institutional, Local PI: Eisai, Genentech, Roche, Exelixis, Pfizer, CRISPR Therapeutics, Allogene Therapeutics; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Leadership Role: SWOG; Other, Other, Travel reimbursement: CRISPR, Roche. B. Beuselinck: Financial Interests, Institutional, Advisory Board, Advisory board: BMS, MSD, AstraZeneca, Ipsen; Financial Interests, Institutional, Advisory Board, Testimony: BMS, MSD; Financial Interests, Institutional, Invited Speaker, Conference: Merck, Pfizer, Ipsen; Financial Interests, Institutional, Research Grant, Research grant for transational research on kidney cancer: BMS. B.E. Szabados: Financial Interests, Personal, Other, travel funding: Roche/Genentech; Financial Interests, Personal, Invited Speaker: MSD, Pfizer; Financial Interests, Personal, Advisory Board: Ellipses, Merck kga, Ipsen. 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. L. Ludwig: Financial Interests, Personal, Full or part-time Employment: Ipsen. 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, 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 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. D.Y.C. Heng: Financial Interests, Personal, Advisory Board: Pfizer, Merck, BMS, Ipsen, Novartis, AstraZeneca, Roche; Financial Interests, Personal, Steering Committee Member: Exilexis; Financial Interests, Institutional, Local PI: BMS, Pfizer, Ipsen. All other authors have declared no conflicts of interest.