Abstract 1455P
Background
Clinical trials of immuno-oncology (IO) agents have demonstrated higher complete response (CR) rates in the IO combination arms. We aimed to characterize patients achieving CR to first-line therapies in real-world settings.
Methods
Using the IMDC, a large multinational observational cohort study, response-evaluable patients who received either first-line IO-based combination therapy (ie, IO/IO doublet or IO/anti-VEGF) or VEGF-targeted monotherapy (ie, sunitinib or pazopanib) were analyzed. Overall survival (OS) was compared based on the best overall response, as per RECIST 1.1.
Results
A total of 52 (4.6%) out of 1126 and 223 (3.0%) out of 7557 patients achieved CR to IO-based and VEGF-targeted therapies, respectively (P = 0.005). An odds ratio (OR) for CR by IO (vs. VEGF) was 1.56 (95% CI 1.11–2.17; P = 0.009) after adjustment for the IMDC risk. Favourable-/intermediate- (vs. poor-) IMDC risk was significantly associated with CR in both the IO and VEGF cohorts, giving respective ORs of 2.97 (95% CI 1.16–7.60; P = 0.024) and 2.37 (95% CI 1.52–3.68; P < 0.001). Among the patients who achieved CR, non-clear cell histology (13.8% and 4.1%; P = 0.016), sarcomatoid dedifferentiation (29.8% and 13.5%; P = 0.014), and multiple sites of metastases (75.6% and 48.2%; P < 0.001) differed significantly across the IO and VEGF cohorts (Table). CR (vs. non-CR) was significantly associated with OS benefit in both the IO and VEGF cohorts, giving respective hazard ratios of 0.08 (95% CI 0.02–0.33; P < 0.001) and 0.17 (95% CI 0.13–0.24; P < 0.001) after adjustment for non-clear cell histology, sarcomatoid dedifferentiation, multiple sites of metastases, and the IMDC risk. Table: 1455P
Cohort characteristics of patients achieving CR
| Variable | Whole cohort | IO cohort | VEGF cohort | P-value | |||
| (n = 275) | (n = 52) | (n = 223) | |||||
| Median age, yr (IQR) | 61 | (54-68) | 61 | (52-67) | 61 | (54-68) | 0.766 |
| Male, n (%) | 211 | (76.7%) | 43 | (82.7%) | 168 | (75.3%) | 0.362 |
| Non-clear cell histology, n (%) | 16 | (5.9%) | 7 | (13.8%) | 9 | (4.1%) | 0.016 |
| Sarcomatoid dedifferentiation, n (%) | 38 | (16.9%) | 14 | (29.8%) | 24 | (13.5%) | 0.014 |
| Multiple sites of metastases, n (%) | 126 | (53.4%) | 34 | (75.6%) | 92 | (48.2%) | <0.001 |
| IMDC risk, n (%) | 0.773 | ||||||
| Favourable | 52 | (22.7%) | 12 | (26.7%) | 40 | (21.7%) | |
| Intermediate | 149 | (65.1%) | 28 | (62.2%) | 121 | (65.8%) | |
| Poor | 28 | (12.2%) | 5 | (11.1%) | 23 | (12.5%) |
Conclusions
The CR rate was higher in the IO cohort. Among the patients achieving CR, some classically unfavourable baseline prognostic features were more frequently observed in the IO cohort. CR was an indicator of favourable OS.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Daniel Y.C. Heng.
Funding
Has not received any funding.
Disclosure
K. Takemura: Financial Interests, Personal, Research Grant, Grants for Research Abroad: The Yasuda Medical Foundation. 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, unpaidhttps://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, Other, Political vote usually as “independent”, not a member of any political party. I am an issue voter: General US Politics; 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; 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; 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). J. 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Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers-Squibb, 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, Bristol Myers-Squibb, Exelixis, Ipsen, Merck, MSD, Seattle Genetics, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai. 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. T. Yuasa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, BMS Japan, MSD. 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.