Abstract 3412
Background
WNT pathway mutations (mut) are uncommon in NSCLC. Recent preclinical studies suggest that APC/CTNNB1 mut induce immune resistance in lung adenocarcinoma but how they may impact on immunotherapy response in the clinics remains unclear. Objective: our aim is to describe the clinical outcomes - Overall survival (OS) and progression-free-survival (PFS) and response rate (RR) - of a metastatic NSCLC cohort with APC/CTNNB1 mut treated with immunotherapy.
Methods
We selected those patients with metastatic NSCLC and APC or CTNNB1 mut detected through Amplicon-Seq (tissue), Foundation (plasma), Guardant (plasma) or exome sequencing (tissue) performed from 2014 to 2018.
Results
Incidence of APC/CTNNB1 mut in NSCLC in our hospital has been 1,26% and 0,7% respectively by Amplicon-Seq (tissue) and 10.4% and 1.04% respectively by exome sequencing (tissue). We identified 27 patients with APC (81%) or CTNNB1 (19%) mutations. The median age of the patients was 59 years (44-74), 72% of them were male and most frequent histology was adenocarcinoma (66%). Fifteen of the patients received ICI, 27% as a first line treatment and 47% as a second line. Interestingly, 1 patient had EGFR mut (exon 19 and 20) and 4 patients had KRAS mut. Median OS of the whole cohort from date of diagnosis was 24.5 months (CI95% 13.7-NA). Median OS was 23.5 months (CI95% 10.4-NA) for those patients who harboured CTNNB1 mut and 57.3 months (CI95% 13.7-NA) for those patients with APC mut (HR 1.8, CI95% 0.32-10, p = 0.5). Median PFS with ICI was 6.6 months (CI95% 0.9-NA). Median PFS was 0.7 months (CI95% 0.5-NA) for those patients with CTNNB1 mut and 8.9 months (CI95% 1.8-NA) with APC mut (HR 6.7, CI95% 1.1-41, p = 0.04). None of the 2 CTNNB1 mut patients responded to ICI, while RR in the APC mut cohort was 30% (4 out of 13).
Conclusions
In our cohort, APC mut did not show to impair clinical outcomes. Few CTNNB1 mut cases hinder conclusive analyses. Correlation with other predictive biomarkers such as tumor mutation burden and PDL1 expression is ongoing.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Vall d´Hebron Institute of Oncology (VHIO).
Funding
Grant from: Carlos III Institute of Health, Madrid, Spain: PI14/01248 and PI17/00938.
Disclosure
P. Iranzo: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Rovi; Advisory / Consultancy: Kyowa Kirin; Advisory / Consultancy, Travel / Accommodation / Expenses: Grunental. A. Callejo: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Kyowa kirin; Travel / Accommodation / Expenses: Celgene. N. Pardo: Advisory / Consultancy: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Boehringer. A. Martinez: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer. A. Navarro: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer; Advisory / Consultancy: Oryzon Genomics; Travel / Accommodation / Expenses: MSD. S. Cedres: Advisory / Consultancy: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer ; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer; Advisory / Consultancy: MSD; Advisory / Consultancy: Amphera. R. Dienstmann: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Symphogen; Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: Amgen; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Servier; Research grant / Funding (institution): Merck. H.G. Palmer: Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Blueprint; Research grant / Funding (institution): Merus; Research grant / Funding (institution): Cellestia. A. Vivancos: Advisory / Consultancy, Research grant / Funding (institution): SYSMEX; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: MERCK; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Guardant Health; Licensing / Royalties, Technology Transfer DX Field: Ferrer; Research grant / Funding (institution): DEBIO; Research grant / Funding (institution): Cellestia; Research grant / Funding (institution): Chittern. E. Felip: Advisory / Consultancy: Abbvie; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Blueprint Medicines; Advisory / Consultancy: Boehringer Ingelheim,; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: Janssen; Advisory / Consultancy: Medscape; Advisory / Consultancy: Merck KGaA; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Takeda; Advisory / Consultancy: Touchtime; Research grant / Funding (institution): Fundación Merck Salud; Research grant / Funding (institution): Grant for Oncology Innovation EMD Serono. All other authors have declared no conflicts of interest.
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