116P - Any regression of tumor (ART) as an intermediate endpoint in patients (pts) treated with immune checkpoint inhibitors (ICI): A pan-cancer analysis

Background

Response to ICI per RECIST 1.1 is durable and associated with improved overall survival (OS). Benefit extends beyond responders to pts with stable disease (SD), who constitute a heterogeneous group with increase or decrease in tumor size without meeting response or progression criteria. We hypothesize that ART may better discriminate benefit translating to improved OS.

Methods

We included 1216 pts with advanced non-small cell lung cancer (NSCLC), melanoma, urothelial carcinoma (UC), esophagogastric cancer (EGC), renal cell carcinoma (RCC), head and neck squamous cell cancer (HNSCC), and colorectal cancer (CRC) treated with ICI. Using Neutrophil-Lymphocyte Ratio (NLR), sites of metastasis, ECOG-performance status, tumor mutation burden, and prior therapy, we conducted Cox proportional hazards models to examine association of ART and RECIST1.1 with OS. Results were validated using bootstrap analyses of 1000 replicates.

Results

We included pts with NSCLC (n=522), melanoma (n=262), UC (n=140), EGC (n=93), RCC (n=83), HNSCC (n=71) and CRC (n=43). Median age was 66 (range 58-73) and 58% were male. Per RECIST, 68 pts (5.6%) had complete response (CR), 277 (22.9%) partial response (PR), 579 (47.7%) progressive disease (PD), and 290 (23.9%) SD. 175 (60.3%) pts with SD had ART. CR+PR (vs SD+PD) was associated with OS (HR=0.3, 95%CI: 0.2-0.4, p<0.001). ART (vs no ART) was significantly prognostic for pts with SD on univariate (HR=0.3, 95%CI: 0.2-0.3, p<0.001) and multivariate analysis (Table). Bootstrap validation corroborated these results (HR=0.5, 95%CI: 0.4-0.7, p<0.001) in NSCLC, melanoma, and UC where >25 pts had SD. Table: 116P

Conclusions

ART is a robust endpoint capturing OS benefit in a larger proportion of pts with advanced solid tumors receiving ICI compared to RECIST 1.1. ART warrants study as a surrogate endpoint in pts without RECIST-measurable disease to enable inclusive trials that expedite drug development and biomarker discovery.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C. Labaki: Financial Interests, Institutional, Research Grant: Genentech/imCORE. 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, 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 1^st 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. G.P. Sonpavde: Financial Interests, Personal, Advisory Board: EMD Serono/Pfizer, Bristol Myers Squibb, Genentech, Merck, Sanofi, Seattle Genetics, AstraZeneca, Exelixis, Janssen, Bicycle Therapeutics, Immunomedics/Gilead, Scholar Rock, G1 Therapeutics, Loxo Oncology, Lucence; Financial Interests, Personal, Advisory Board, Editor of Bladder Cancer Virtual Center of Excellence for Practice Update: Elsevier; Financial Interests, Personal, Other, Member of data safety monitoring board: Mereo; Financial Interests, Personal, Other, Author of chapter: Uptodate; Financial Interests, Personal, Invited Speaker: Medscape, Research to practice, Onclive, Physicians Education Resource, Debiopharm; Financial Interests, Institutional, Research Grant: Sanofi, AstraZeneca, Gilead, QED, Predicine, EMD Serono; Non-Financial Interests, Principal Investigator, Steering committee of trial: Bristol Myers Squibb; Non-Financial Interests, Principal Investigator: G1 Therapeutics; Non-Financial Interests, Leadership Role, steering committee of trial: QED; Other, Spouse employment: Myriad Genetics. All other authors have declared no conflicts of interest.