Abstract 4111
Background
Molecular heterogeneity drives tumour evolution and resistance to therapies. Because of biopsy challenges in non-small cell lung cancer (NSCLC), few studies compared the molecular profile between primary tumour (PT) and metastasis (Met). Here, we compare somatic single-nucleotide variants (SNVs), tumour mutational burden (TMB) and expression profiles between PT and matched metachronous Met in NSCLC patients (pts).
Methods
DNA and RNA were extracted from 14 matched fresh-frozen samples and PBMCs from 7 pts treated at the Institut d’Oncologie Thoracique (Gustave Roussy, GR) between 2011 and 2015. GATK4 Mutect2 were used for SNV calling and TMB on whole exome sequencing. Salmon was used for expression counts from RNAseq; Z-scores were computed by comparing data to 158 other NSCLC RNAseq from GR molecular profiling trials; GSVA R package was use to assess single sample gene set enrichment score (ssGSEA).
Results
Median age was 67 yo (62-78); 4/7 metastases were biopsied after chemotherapy; histology was adenocarcinoma (6) or large cell carcinoma (1). The median number of SNVs unique to PT or Met was 50 (10-143) or 79 (36-324), respectively; it was 65 (0-110) for shared SNVs; 6/7 pts had known driver alterations (TP53, KRAS, PIK3CA) in both lesions; one Met acquired a pathogenic KRAS G35C mutation. Median TMB was 3.9 (0.3-4.3) in PT and 4.1 (2.2-8.4) in Met. Genes with top negative Z-scores (MRFAP1, EP400, RIOX1, DDX27) were shared between PT and Met in 6/7 pts; genes with top positive Z-score were unique. ssGSEA-enriched genesets were shared between PT and Met; top enriched hallmarks included Myc targets, Mitotic Spindle, DNA repair, oxidative phosphorylation and TGFb signaling.
Conclusions
Matched comparison of molecular profiles between PT and Met evidence shared and unique alterations; this informs on tumor evolution and may help guiding treatment choice.
Clinical trial identification
Editorial acknowledgement
AK: AK was funded by the DUERTECC Gustave Roussy program
LCD: LCD was funded by the INSERM ATIP-Avenir grant from SPV
Legal entity responsible for the study
Sophie Postel-Vinay.
Funding
Cancéropole d’Ile de France.
Disclosure
A Kawachi: Funded by the DUERTECC Gustave Roussy program. L. Colmet-Daage: Funded by the INSERM ATIP-Avenir grant from SPV. L. Verlingue: Honoraria (self): Adaptherapy; Research grant / Funding (self): Bristol-Myers Squibb. D. Planchard: Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Celgene; Honoraria (self): Eli Lilly; Honoraria (self): Merck; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): prIME Oncology; Honoraria (self): Peer CME; Honoraria (self): Roche; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: Boehringer Ingelheim ; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: prIME Oncology; Travel / Accommodation / Expenses: Pfizer. A. Hollebecque: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Janssen Cilag; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi. C. Massard: Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): BMS; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Janssen Cilag; Research grant / Funding (self): Merck, Novartis; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Roche; Research grant / Funding (self): Sanofi; Advisory / Consultancy: Amgen; Advisory / Consultancy: Astellas; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: BeiGene; Advisory / Consultancy: BMS; Advisory / Consultancy: Celgene; Advisory / Consultancy: Debiopharm; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Janssen; Advisory / Consultancy: Lilly. B. Besse: Research grant / Funding (self): Abbvie; Research grant / Funding (self): Amgen; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Biogen; Research grant / Funding (self): Blueprint Medicines; Research grant / Funding (self): BMS; Research grant / Funding (self): Celgene; Research grant / Funding (self): Eli Lilly; Research grant / Funding (self): GSK; Research grant / Funding (self): Ignyta; Research grant / Funding (self): IPSEN; Research grant / Funding (self): Merck KGaA; Research grant / Funding (self): MSD; Research grant / Funding (self): Nektar; Research grant / Funding (self): Onxeo; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Pharma Mar; Research grant / Funding (self): Sanofi; Research grant / Funding (self): Spectrum Pharmaceuticals; Research grant / Funding (self): Takeda. J. Soria: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Astex; Advisory / Consultancy: Clovis; Advisory / Consultancy: GSK; Advisory / Consultancy: GamaMabs; Advisory / Consultancy: Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Mission Therapeutics; Advisory / Consultancy: Merus; Advisory / Consultancy: Pfizer; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Servier; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Takeda; Full / Part-time employment: AstraZeneca. S. Postel Vinay: Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): BMS; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Janssen Cilag; Research grant / Funding (self): Merck; Research grant / Funding (self): Novartis; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Roche; Research grant / Funding (self): Sanofi. All other authors have declared no conflicts of interest.
Resources from the same session
4543 - Long-term real-world (RW) outcomes in patients with advanced melanoma (MEL) treated with ipilimumab (IPI) and non-IPI therapies: IMAGE study
Presenter: Stéphane Dalle
Session: Poster Display session 3
Resources:
Abstract
4523 - Prognostic Factors for efficacy of Ipilimumab used after AntiPD1 and/or BRAF+MEK inhibitors in Melanoma Patients: an Italian Melanoma Intergroup study
Presenter: Riccardo Marconcini
Session: Poster Display session 3
Resources:
Abstract
3632 - Rechallenge with combination ipilimumab and anti-PD-1 (IPI+PD1) in metastatic melanoma after acquired resistance to IPI+PD1 immunotherapy
Presenter: Adriana Hepner
Session: Poster Display session 3
Resources:
Abstract
3732 - Clinicopathologic characteristics of immune colitis in melanoma patients treated with combination ipilimumab and anti-PD1 (IPI+PD1) and PD1 monotherapy.
Presenter: Kazi Nahar
Session: Poster Display session 3
Resources:
Abstract
5005 - Real-world outcomes of ipilimumab plus nivolumab for advanced melanoma in the Netherlands
Presenter: Michiel van Zeijl
Session: Poster Display session 3
Resources:
Abstract
5524 - Utilization of Real-World Data to Assess the Effectiveness of Immune Checkpoint Inhibitors (ICIs) in Elderly Patients with Metastatic Melanoma
Presenter: D Scott Ernst
Session: Poster Display session 3
Resources:
Abstract
5884 - Tumor mutational burden and response to PD-1 inhibitors: an analysis of 89 cases of metastatic melanoma.
Presenter: Léa Dousset
Session: Poster Display session 3
Resources:
Abstract
3120 - Increase in S100B and LDH as early outcome predictors for non-responsiveness to anti-PD-1 monotherapy in advanced melanoma.
Presenter: Elisa Rozeman
Session: Poster Display session 3
Resources:
Abstract
2157 - Immune status defined by molecular information layers predicts response to pembrolizumab treatment in advanced melanoma
Presenter: Guillermo Prado-Vázquez
Session: Poster Display session 3
Resources:
Abstract
2553 - Interim analysis of a phase Ib study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild type melanoma progressing on prior anti-PD-L1 therapy
Presenter: Shahneen Sandhu
Session: Poster Display session 3
Resources:
Abstract