Abstract 252P
Background
Real-world progression-free survival (rwPFS) and time to next line of therapy (TTNT) are two endpoints of clinical interest in patients with metastatic breast cancer (MBC). Their validation as intermediate endpoints for overall survival (OS), in a real-world setting, remains not fully established.
Methods
We conducted a retrospective cohort study using the nationwide US Electronic Health Record-derived de-identified Flatiron Health database. The study population included pts diagnosed with MBC from Jan 1, 2011 through Feb 30, 2021. Kendall tau correlation between each surrogate endpoint (rwPFS and TTNT) and OS was evaluated using the Hougaard copula model. Kendall’s tau (τ) was calculated in the full cohort, and within each subgroup of metastatic disease, based on their prognostic significance, as defined by the occurrence of bone metastases (mets) only (subgroup 1), non-hepatic visceral mets +/- bone mets (subgroup 2), liver mets +/- other visceral and/or bone mets (subgroup 3), and one or more brain mets +/- other types of metastasis (subgroup 4). This work was supported by the imCORE network.
Results
Overall, 9,733 patients with MBC were included. Median age was 63 years (IQR: 54-72). Regarding sites of metastatic disease, subgroup 2 was most highly represented (n=4,188; 43.0%), followed by subgroup 1 (n=2,601; 26.7%), subgroup 3 (n=2,306; 23.7%) and subgroup 4 (n=638; 6.6%). Median OS in the overall population was 32.4 mos (95%CI: 31.2-33.3). Median rwPFS was 11.5 mos (95%CI: 11.1-11.9), and median TTNT was 11.1 mos (95%CI: 10.7-11.5). In the full cohort, the correlation of rwPFS with OS was 0.54, while that of TTNT with OS was 0.47 (Table). Table: 252P
Median OS, rwPFS and TTNT and Kendall tau correlation of each pair of evaluated endpoints.
| Overall Population (n=9,733) | Subgroup 1 (n=2,601) | Subgroup 2 (n=4,188) | Subgroup 3 (n=2,306) | Subgroup 4 (n=638) | |
| Median OS, months (95%CI) | 32.4 (31.2-33.3) | 44.3 (42.2-46.9) | 32.7 (31.0-34.0) | 22.6 (21.3-24.4) | 16.6 (14.8-19.7) |
| Median rwPFS, months (95%CI) | 11.5 (11.1-11.9) | 18.5 (16.9-19.4) | 11.9 (11.4-12.7) | 8.2 (7.7-8.9) | 5.9 (4.9-6.7) |
| Median TTNT, months (95%CI) | 11.1 (10.7-11.5) | 16.2 (15.1-17.9) | 11.3 (10.6-12.0) | 8.7 (8.2-9.2) | 6.7 (5.7-7.6) |
| rwPFS-OS Correlation: τ (95%CI) | 0.54 (0.53-0.56) | 0.47 (0.45-0.50) | 0.54 (0.52-0.56) | 0.57 (0.55-0.59) | 0.60 (0.56-0.64) |
| TTNT-OS Correlation: τ (95%CI) | 0.47 (0.46-0.48) | 0.37 (0.34-0.40) | 0.45 (0.43-0.46) | 0.54 (0.52-0.56) | 0.58 (0.55-0.62) |
Conclusions
Real-world PFS (rwPFS) and TTNT may represent meaningful intermediate endpoints for OS in patients with MBC overall, and within different disease subgroups.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
imCORE network.
Funding
Genentech/imCORE.
Disclosure
C. Labaki: Financial Interests, Institutional, Research Grant: Genentech/imCORE. Z. Bakouny: Non-Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Genentech/ imCORE; Financial Interests, Personal, Writing Engagements: UpToDate. T. Sanglier: Financial Interests, Personal, Project Lead: F. Hoffmann-La Roche; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche. A. Schmidt: Financial Interests, Personal, Invited Speaker: Astellas. D.A. Braun: Financial Interests, Personal, Invited Speaker, Speaker on innovation in oncology and clinical trial design: LM Education/Exchange Services; Financial Interests, Personal, Other, Consulting: Octane Global, Defined Health, Adept Field Solutions, Slingshot Insights, Blueprint Partnerships, Charles River Associates, Trinity Group, Insight Strategy, Catenion; Financial Interests, Personal, Advisory Board, Advisory Board: Exelixis, AVEO; Non-Financial Interests, Advisory Role: Bristol-Myers Squibb. F. Bouquet: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-LaRoche; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-LaRoche. W. Xie: Financial Interests, Personal, Other, Consulting: Convergent Therapeutics, Inc. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Novartis, Gilead, Genentech/Roche, Eisai, Sanofi, SeaGen, Daichii Sankyo, 4D Pharma, Puma, ARC Therapeutics; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Other, Consultant: Nektar, Nanostring, Athenex, Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol-Myers Squibb, OncoPep, OncoSec, Certara, Mersana Therapeutics, Ellipses Pharma; Financial Interests, Personal, Advisory Board, Ad board participant/consultant/DSMC: Odonate; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Invited Speaker, Invited speaker for pharma supported educational activity: Chugai Pharmaceuticals; Financial Interests, Personal, Advisory Board, Advisory board participant: G1 Therapeutics; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Personal, Advisory Board, Advisory Board participation: Zentalis, OncXerna; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Institutional, Funding: AstraZeneca, Eli Lilly, Pfizer, Sanofi, SeaGen, Odonate, Cyclacel, Exelixis, Gilead, Bristol Myers Squibb, Eisai, Merck, Novartis, Nektar, Genentech/Roche; Financial Interests, Personal and Institutional, Invited Speaker: CytomX. 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 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, 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. All other authors have declared no conflicts of interest.