1707P - A plasma proteomic based algorithm is associated with prognosis in renal cell carcinoma

Background

PROphetNSCLC is a commercially available pretreatment plasma proteomic model that predicts clinical benefit from first-line PD-(L)1 inhibitor-based therapy in patients with metastatic non-small cell lung cancer (NSCLC). However, it is unknown whether the predictive value of PROphetNSCLC generalizes to other tumor types. We explored the capabilities of PROphetNSCLC in patients with renal cell carcinoma (RCC) treated with TKI inhibitors (VEGFR TKI), immune-checkpoint inhibitors (ICI), or both.

Methods

Pre-treatment plasma samples and retrospective clinical data were collected from patients with RCC (n=201) treated with VEGFR TKI (n=76), ICI (n=68), or anti-VEGF + ICI combination therapies (n=57). Patients were assigned a PROphet-positive or -negative result based on computational analysis of SomaScan-derived proteomic profiles in pre-treatment plasma samples. Kaplan-Meier survival analysis and Cox proportional hazards models compared overall survival (OS) and progression-free survival (PFS) in the PROphet-positive and PROphet-negative groups.

Results

Among RCC patients, PROphet-positive patients (n=143) had improved OS versus PROphet-negative patients (n=58; median OS 57.5 months vs 18.4 months, HR=0.22, 95% CI: 0.14-0.35, p<0.0001). This OS difference remained significant after adjustment for treatment type and International Metastatic Database Consortium (IMDC) risk factors (HR=0.21, 95% CI: 0.12-0.34, p<0.0001). PROphet-positive patients also had improved PFS versus PROphet-negative patients (median PFS 15.6 months vs. 8.3 months, HR=0.59, 95% CI: 0.40-0.89, p=0.01). Exploratory analyses identified distinct subsets of circulating proteins associated with clinical benefit among patients treated with VEGFR TKI versus ICI therapies.

Conclusions

A proteomic machine learning model previously trained to predict the outcomes to ICI therapy in NSCLC was also associated with clinical outcomes in patients with RCC. This suggests that some proteomic features associated with prognosis are shared between NSCLC and RCC. Further analyses are underway to describe the specific model features and biological pathways associated with the response to VEGFR TKI versus ICI therapy among patients with RCC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Oncohost.

Disclosure

E. Saad: Financial Interests, Institutional, Research Funding: Roche Genentech. C. Lahav: Financial Interests, Personal, Full or part-time Employment: OncoHost; Financial Interests, Personal, Stocks/Shares: OncoHost. M. Harel: Financial Interests, Personal, Full or part-time Employment: OncoHost; Financial Interests, Personal, Stocks/Shares: OncoHost; Non-Financial Interests, Institutional, Proprietary Information: OncoHost. G. Loewenthal: Financial Interests, Personal, Full or part-time Employment: OncoHost; Financial Interests, Personal, Stocks/Shares: OncoHost. S. Raveh Shoval: Financial Interests, Personal, Full or part-time Employment: OncoHost; Financial Interests, Personal, Stocks/Shares: OncoHost. I. Sela: Financial Interests, Personal, Full or part-time Employment: OncoHost; Financial Interests, Personal, Stocks/Shares: OncoHost. A. Dicker: Financial Interests, Personal, Advisory Board: OncoHost, Janssen, CVS, Aptar; Financial Interests, Personal, Stocks/Shares: OncoHost; Non-Financial Interests, Leadership Role: NRG Oncology; Non-Financial Interests, Principal Investigator: Prostate Cancer Foundation; Non-Financial Interests, Advisory Role: National Cancer Institute. Y. Elon: Financial Interests, Personal, Full or part-time Employment, CTO: OncoHost; Financial Interests, Personal, Stocks/Shares: OncoHost. 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, Advisory Board, GU cancer drug development: alkermes, Gilead; Financial Interests, Personal, Other, Study section reviewer. $200.00 per day for 1 day: National Cancer Institute; Financial Interests, Personal, Other, Cancer Center Grand Rounds: Cleveland Clinic; Financial Interests, Personal, Advisory Board, Advisory Board/month: CURESPONSE; Financial Interests, Personal, Advisory Board: Tempest, Precede Bio (not publicly traded)); 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, advisor: Pionyr (not publicly traded), Tempest (publicly traded), Osel (not publicly traded), Precede Bio (not publicly traded)), CURESPONSE (not publicly traded), Inndura; Financial Interests, Personal, Stocks/Shares: Primium; 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; Financial Interests, Institutional, Local PI, National Chair: Roche; Financial Interests, Institutional, Funding, National co-chair: Pfizer, EMD-Serono; Financial Interests, Institutional, Funding, Chair of trial: Lilly; Financial Interests, Institutional, Local PI: Surface Oncology, GSK; 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- current and BOD member (unpaid): 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, The institution filed patents related to biomarkers of immune checkpoint blockers, and circulating tumor DNA. No money made and some patents were abandoned: Filed patents. W. Xu: Financial Interests, Personal, Advisory Board: Exelixis, Xencor, Jazz; Financial Interests, Personal, Other, Consulting: Aveo, Merck; Financial Interests, Institutional, Research Grant, Research funding paid to institution: Oncohost; Financial Interests, Institutional, Local PI: CRISPR Therapeutics. All other authors have declared no conflicts of interest.