Abstract 1502
Background
Overall survival (OS) is the most relevant endpoint for evaluation of checkpoint inhibitors (CPI). Identification of early surrogates of OS is important to inform early clinical efficacy signals and treatment decisions. Here, we evaluated multiple metrics of circulating tumor DNA (ctDNA) for association with OS in the Ph3 OAK study, which demonstrated clinically significant OS benefit in ≥ 2L NSCLC patients treated with atezolizumab vs docetaxel.
Methods
Plasma from 94 patients taken at baseline and at subsequent cycles of therapy every three weeks (C2D1, C3D1, and C4D1) were analyzed retrospectively for ctDNA with the AVENIO ctDNA Surveillance Kit* (Jiang et al., 2018). Mutations detected in matched PBMC DNA were excluded in correlation analyses with clinical outcomes (Yaung et al., 2019). ctDNA was measured by allele frequency (AF) or mutant molecules per milliliter (MMPM), and summarized across multiple mutations within a sample by median, mean or maximum. Concordance between these per-sample metrics and PFS/OS were assessed using C index, which is equivalent to AUC under a Receiver Operating Characteristic (ROC) curve. *For Research Use Only; Not for use in diagnostic procedures.
Results
Using absolute and relative change from baseline of these metrics showed various levels of association with OS for both treatment arms (atezolizumab arm C index average 0.63, range 0.47 -0.76 and docetaxel arm C index average 0.50, range 0.39 - 0.61). As noted, maximal MMPM at C3D1 or 6 weeks had comparable association with OS in both treatment arms (atezolizumab arm C index = 0.74 and docetaxel arm C index = 0.73). Dichotomized at a median of 8.75 maximal MMPM, KM curves showed the 1-year survival rate in the atezolizumab arm among MMPM low vs high patients was 0.81 vs 0.43; and in the docetaxel arm was 0.7 vs 0.07. Associations with PFS tended to be weaker than those for OS.
Conclusions
Overall ctDNA levels were associated with OS in 2L+ NSCLC. ctDNA may be a promising non-invasive blood based biomarker in the metastatic setting of NSCLC and warrants further studies to demonstrate its utility in clinical development.
Clinical trial identification
OAK (NCT02008227).
Editorial acknowledgement
Legal entity responsible for the study
Roche.
Funding
Roche.
Disclosure
D.R. Gandara: Advisory / Consultancy: AstraZeneca, Celgene, CellMax Life, FujiFilm, Roche-Genentech, Guardant Health, Inviata, IO Biotech, Lilly, Liquid Genomics, Merck, Samsung Bioepis, Pfizer; Research grant / Funding (institution), Research grants : Bristol-Myers Squib, Roche-Genentech, Novartis, Merck. W. Zou: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. J. Jiang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. S. Yaung: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. F. Fuhlbrück: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. J. Wu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. M. Peterson: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. J. Palma: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. M. Ballinger: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. E. Peters: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. D. Shames: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche. N. Patil: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche.
Resources from the same session
592 - Effects of novel targeted anticancer drugs on cytotoxicity, apoptosis, angiogenesis, EMT, drug resistance and autophagic mechanism
Presenter: Seyma Aydinlik
Session: Poster Display session 1
Resources:
Abstract
3235 - Delineating the mechanisms of alpha 1-3 fucosyltransferase FUT11 in ovarian cancer
Presenter: Qi Chen
Session: Poster Display session 1
Resources:
Abstract
3577 - The tyrosine kinase inhibitor Dasatinib blocks tumor growth, invasion and recurrence potential by interrupting the communication between cancer cells and their surrounding microenvironment in triple negative breast cancer
Presenter: Miriam Nuncia-Cantarero
Session: Poster Display session 1
Resources:
Abstract
4808 - NORE1A induces a feedback termination of TNF signaling by antagonizing TNFR1 through ITCH-mediated destruction complex
Presenter: Jieun Ahn
Session: Poster Display session 1
Resources:
Abstract
1294 - Hsp90 inhibitors enhance the antitumoral effect of osimertinib and overcome osimertinib resistance in non-small-cell cell lung cancer cell models
Presenter: Jordi Codony-Servat
Session: Poster Display session 1
Resources:
Abstract
1559 - Expression of IL-17RA promotes cancer stem-like properties of colorectal cancer cells by Stat3 activation
Presenter: Chih-Yung Yang
Session: Poster Display session 1
Resources:
Abstract
1615 - Adaption of Pancreatic Cancer Cells to AKT1 Inhibition Induces the Acquisition of Cancer Stem-Cell Like Phenotype Through Upregulation of Mitochondrial Functions
Presenter: Hugo Arasanz
Session: Poster Display session 1
Resources:
Abstract
4793 - Bub3 is phosphorylated by the Ataxia-Telangiectasia Mutated Kinase in mitosis and required for activation of the mitotic spindle checkpoint in Breast Cancer
Presenter: Mingming Xiao
Session: Poster Display session 1
Resources:
Abstract
1448 - The regulation of INK4 locus by long non-coding RNAs
Presenter: Yojiro Kotake
Session: Poster Display session 1
Resources:
Abstract
1858 - Vascular Endothelial Growth Factor in Colorectal Cancer Pathology, Survival and Treatment
Presenter: Liz Baker
Session: Poster Display session 1
Resources:
Abstract