In advanced NSCLC, ctDNA is an emerging tool in molecular profile testing at diagnosis and at resistance to targeted therapies. However, for CNS limited mts, ctDNA might have a reduced accuracy because of low concentrations. Aim: to assess feasibility of ctDNA in NSCLC with isolated CNS disease/progression (PD) (iCNS).
This is a retrospective analysis of consecutive advanced NSCLC pts treated at Gustave Roussy from 01.2016 to 06.2018 included in 2 prospective studies (CEC-CTC, MSN). Included: any molecular tissue alteration at baseline (EGFR, ALK, BRAF, KRAS, HER2, ROS1, MET, TP53), CNS disease and ≥1 ctDNA sample at diagnosis/PD. CtDNA was performed by next generation sequencing (NGS- InVisionSeq™-Lung). Clinical/molecular/imaging data were collected. CtDNA in iCNS group were compared to systemic PD group (with CNS PD or stable disease, S-CNS). ctDNA was defined as positive if ≥ 1 mutation in the NGS panel.
422/959 screened pts had ≥1 ctDNA sample. 183/422 pts had CNS disease. 58/182 pts had ctDNA sample at time of CNS disease and 66 samples were eligible for inclusion: 21 iCNS and 45 S-CNS (≥1 sample/patient as ≥ 1 PD). In iCNS and S-CNS, pts characteristics were: median age 55 vs 59 years, female gender 94% vs 59%, adenocarcinoma histology 100% vs 93%, smoking history 35% vs 44%, median mts sites at diagnosis 1 vs 2. Prevalence of EGFR mutation at diagnosis was 76 and 61%, ALK rearrangement 18 and 10%, KRAS 6 and 5% in iCNS and in S-CNS, respectively. HER2, TP53, BRAF and MET alterations were present only in S-CNS group (12%, 10%, 5% and 2%). CtDNA was positive in 38% in iCNS vs. 98% in S-CNS groups (Fisher test, p < 0.0001) (Table).
In NSCLC pts with isolated CNS involvement, genomic alterations assessed by ctDNA in plasma had a low detection rate. (Table).
Gustave Roussy Institute, Villejuif, France.
Has not received any funding.
L. Mezquita: Consulting, advisory role: Roche Diagnostics; Lectures, educational activities: Bristol-Myers Squibb, Tecnofarma, Roche, AstraZeneca; Travel, accommodations, expenses: Chugai. D. Planchard: Consulting, advisory role or lectures: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Clinical trials research: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo. C. Morris, E. Green: Employee, shareholder: Inivata. B. Besse: Sponsored research at Gustave Roussy Cancer Center: AbbVie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma; Investigator or co-investigator of trials: Nerviano, GSK, Pfizer, Roche-Genentech, Lilly, OSE Pharma, MSD, Celgene, Stemcentrx, Ignyta, AbbVie, Loxo Oncology, AstraZeneca, Blueprint Medicines. All other authors have declared no conflicts of interest.