Abstract 886P
Background
Immuno-oncology agents (IO) have become a standard-of-care in the treatment of R/M HNSCC, however only a subset of patients (pts) benefit. Liquid biopsy offers access to circulating tumor DNA (ctDNA); currently data on ctDNA kinetics under treatment selection pressure is limited.
Methods
R/M HNSCC pts treated with either platinum-based chemotherapy (CT) or IO, anti-PD1/L1 (+/- second IO) underwent serial ctDNA collection pre-cycles 1/2/3 and upon disease progression, timepoints (T) 1-4 (NCT03712566). Error-corrected sequencing using a SCC-optimised panel was applied at each available T. After filtering out clonal hematopoiesis-associated mutations, mean variant allele frequency (VAF) was calculated per T. Median ctDNA abundance determined ctDNA groupings and changes were correlated with progression free survival (PFS) and overall survival (OS).
Results
Of the 36 eligible pts (received >=1 cycle) 27 received IO and 9 CT. Median age was 64 (20-82), 67% were male, 72% prior smokers and 92% ECOG PS 1. Median PFS and OS were 2.3 mo (95% CI 0.7-11.2) and 6.9 mo (95% CI 1.9-28) respectively. OS was significantly better in IO treated pts, 6.1 vs 3.9 mo (p = 0.01). Twenty-eight pts (21 IO) had somatic mutations detected at T1. The most frequent TP53 (24%), CDKN2A (16%), FRG1B (14%) and KMT2D (11%). ctDNA abundance at T1 correlated with PFS/OS in both univariate (p = 0.02, p = 0.02) and multivariate cox models (HR 3.22 (1.11-9.38) p = 0.03, HR 3.64 (1.23-10.73) p = 0.02), adjusted for age, gender, treatment, smoking and HPV. Persistence in VAF at T2 correlated significantly with PFS (HR 3.36 (1.50-7.54) p <0.01) and OS (HR 4.62 (1.93-11.06) p <0.01) respectively. Decrease in Δ VAF (T1-2) identified pts with longer OS, despite early radiological progression (Table). Table: 886P
| N=27 | ΔVAF Decrease T1-T2 | ΔVAF Increase T1-2 | Median OS (mOS) HR (95% CI; p-value) |
| CR/PR/SD>=4cycles | (A) n=4 [4 IO] (mOS = 20.1mo) | (B) n=3 [3 IO] (mOS = 14.4mo) | HR [A vs B] = 1.32 95% CI = 0.22-7.69 p = 0.77 |
| PD/SD<4cycles | (C) n=10 [8 IO] (mOS = 4.8mo) | (D) n=10 [6 IO] (mOS = 3.3mo) | HR [C vs D] = 0.34 95% CI = 0.13-0.90 p = 0.03 |
Conclusions
Low ctDNA abundance at baseline and non-persistence on treatment correlated with improved PFS and OS. Early changes in ctDNA after first treatment may help predict pt outcome beyond RECIST 1.1.
Clinical trial identification
NCT03712566.
Editorial acknowledgement
Legal entity responsible for the study
University Health Network.
Funding
BMO Chair in Precision Cancer Genomics, Ontario Institute for Cancer Research.
Disclosure
M. Oliva: Financial Interests, Personal, Other, Podcast: Merck; Financial Interests, Personal, Invited Speaker, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: MSD. A. Spreafico: Financial Interests, Personal and Institutional, Sponsor/Funding, Consulting: Merck; Financial Interests, Personal and Institutional, Sponsor/Funding, Consulting: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Oncorus; Financial Interests, Personal and Institutional, Sponsor/Funding, Consulting: Janssen/Johnson & Johnson; Financial Interests, Institutional, Sponsor/Funding: Novartis; Financial Interests, Institutional, Sponsor/Funding: Symphogen; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca/Medimmune; Financial Interests, Institutional, Sponsor/Funding: Bayer; Financial Interests, Institutional, Sponsor/Funding: Surface Oncology; Financial Interests, Institutional, Sponsor/Funding: Northern Biologics; Financial Interests, Institutional, Sponsor/Funding: Roche; Financial Interests, Institutional, Sponsor/Funding: Regeneron; Financial Interests, Institutional, Sponsor/Funding: Alkermes; Financial Interests, Institutional, Sponsor/Funding: Array Biopharma/Pfizer; Financial Interests, Institutional, Sponsor/Funding: GSK; Financial Interests, Institutional, Sponsor/Funding: Treadwell. A.R. Hansen: Financial Interests, Personal and Institutional, Sponsor/Funding, Consulting: Merck; Financial Interests, Personal and Institutional, Sponsor/Funding, Consulting: GSK; Financial Interests, Personal and Institutional, Sponsor/Funding, Consulting: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Institutional, Sponsor/Funding: Karyopharm Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Boehringer Ingelheim; Financial Interests, Institutional, Sponsor/Funding: Roche/Genentech; Financial Interests, Institutional, Sponsor/Funding: Janssen; Financial Interests, Institutional, Sponsor/Funding: AZ/Medimmune; Financial Interests, Institutional, Sponsor/Funding: Astellas Pharma; Financial Interests, Institutional, Sponsor/Funding: Macrogenics. R. Jang: Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal and Institutional, Sponsor/Funding, Advisory Role: Novartis; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Institutional, Sponsor/Funding: Merck; Financial Interests, Institutional, Sponsor/Funding: Lilly; Financial Interests, Institutional, Sponsor/Funding: Boston Biomedical ; Financial Interests, Institutional, Sponsor/Funding: Bristol Myers Squibb. V.M. Coyle: Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Institutional, Sponsor/Funding: Bayer; Financial Interests, Institutional, Sponsor/Funding: CellCentric; Financial Interests, Institutional, Sponsor/Funding: Astex Pharmaceuticals ; Financial Interests, Personal, Other, Spouse Honoraria: Gilead Sciences. M. Lawler: Financial Interests, Personal and Institutional, Research Grant, Education grant, Honoraria: Pfizer; Financial Interests, Personal, Invited Speaker, Honoraria: EMD; Financial Interests, Personal, Invited Speaker, Honoraria: Roche; Financial Interests, Personal, Invited Speaker, Honoraria: Carnall Farrar. E. Elimova: Financial Interests, Institutional, Advisory Board, Research Grants: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Board, Research Grants: Zymeworks; Financial Interests, Institutional, Advisory Role: Adaptimmune; Other, Personal, Other, Spouse employee: Merck Vaccines. S.V. Bratman: Financial Interests, Personal, Ownership Interest, Co-founder, patents: DNAMx ; Financial Interests, Institutional, Funding: Nektar Therapeutics ; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Royalties, Patent: Roche. L.L. Siu: Financial Interests, Personal, Advisory Board: Arvinas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: GeneSeeq; Financial Interests, Personal, Advisory Board: Janpix; Financial Interests, Personal, Advisory Board: Loxo; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Morphosys; Financial Interests, Personal, Advisory Board: Navire; Financial Interests, Personal, Advisory Board: Oncorus; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Relay Therapeutics; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Rubius; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Symphogen; Financial Interests, Personal, Advisory Board: Tessa; Financial Interests, Personal, Advisory Board: Voronoi; Financial Interests, Personal, Other, Spouse is co-founder: Treadwell Therapeutics; Financial Interests, Personal, Stocks/Shares, Spouse has stock ownership: Agios; Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: Astellas; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Avid; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: Boerhinger-Ingelheim; Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb; Financial Interests, Institutional, Principal Investigator: GSK; Financial Interests, Institutional, Principal Investigator: Intensity Therapeutics; Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Institutional, Principal Investigator: Mirati; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Roche/Genentech ; Financial Interests, Institutional, Principal Investigator: Shattucks; Financial Interests, Institutional, Principal Investigator: Symphogen. All other authors have declared no conflicts of interest.