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
5103 - CANOPY phase 3 program: Three studies evaluating canakinumab in patients with non-small cell lung cancer (NSCLC)
Presenter: Luis Paz-Ares
Session: Poster Display session 1
Resources:
Abstract
3666 - The Elderly Patient Individualized Chemotherapy (EPIC) trial, a study for an aged population of non-small cell lung cancer.
Presenter: Francesco Passiglia
Session: Poster Display session 1
Resources:
Abstract
4799 - KEYNOTE-495/KeyImPaCT: A Randomized, Biomarker-Directed, Phase 2 Trial of Pembrolizumab-Based Therapy for Non–Small Cell Lung Cancer (NSCLC)
Presenter: Martin Gutierrez
Session: Poster Display session 1
Resources:
Abstract
6035 - Safety, tolerability and activity of autologous T cells with enhanced T-cell receptors specific to NY ESO 1/LAGE 1a (GSK3377794) alone, or in combination with pembrolizumab, in advanced non small cell lung cancer: A Phase 1b/2a randomised pilot study
Presenter: Karen Reckamp
Session: Poster Display session 1
Resources:
Abstract
2176 - IFCT-1701 DICIPLE: a randomized phase 3 trial comparing continuation Nivolumab-Ipilimumab doublet immunotherapy until progression versus observation in patients with PDL1-positive stage IV Non-Small Cell Lung Cancer (NSCLC) after Nivolumab-Ipilimumab induction treatment
Presenter: Gerard Zalcman
Session: Poster Display session 1
Resources:
Abstract
2352 - ATALANTE-1 randomized phase 3 trial, OSE-2101 versus standard treatment as second or third line in HLA-A2 positive advanced non-small cell lung cancer (NSCLC) patients
Presenter: Enriqueta Felip
Session: Poster Display session 1
Resources:
Abstract
2451 - Phase Ib dose-escalation/expansion study of BI 836880, a VEGF/Ang2-blocking nanobody®, in combination with BI 754091, an anti-PD-1 antibody, in patients with advanced solid tumours
Presenter: Nicolas Girard
Session: Poster Display session 1
Resources:
Abstract
4285 - Radiosurgery followed by Tumor Treating Fields (TTFields) for brain metastases (1-10) from NSCLC in the phase 3 METIS trial
Presenter: Minesh Mehta
Session: Poster Display session 1
Resources:
Abstract
4909 - Nivolumab plus ipilimumab (NI) versus chemotherapy plus nivolumab (CN) in squamous cell lung cancer (SqCLC): the SQUINT trial
Presenter: Lorenza Landi
Session: Poster Display session 1
Resources:
Abstract
4125 - DUBLIN-3, a Stage IIIb/IV NSCLC Phase (Ph)3 Trial Comparing the Plinabulin (P)/Docetaxel(D) Combination with D Alone
Presenter: Ramon Mohanlal
Session: Poster Display session 1
Resources:
Abstract