Abstract 1267P
Background
The comprehensive genomic profile by next generation sequencing (NGS) of circulating tumour DNA (ctDNA) can identify a wide spectrum of genomic alterations (GAs) in non-small cell lung cancer (NSCLC). We aimed to assess the clinical utility of amplicon-based ctDNA NGS for detecting GAs and resistance mutations at time of progression (PD).
Methods
Patients (pts) with advanced NSCLC harbouring EGFR mutations (m), ALK rearrangements (r) and BRAFV600Em were prospectively enrolled at tyrosine-kinase inhibitors (TKI) failure in the Liquid Biopsy Program at Gustave Roussy between Nov/15-May/19. Plasma ctDNA was collected at time of PD and analyzed using InVisionFirst®-Lung. The detection rate of driver and resistance GAs on ctDNA were evaluated, as well as the clinically informative results (at least 1 mutation at EGFR/ALK-TKI failure) used for treatment tailoring.
Results
A total of 222 samples were assessed from 134 pts: 58% were females, 52% non-smokers, with median age of 62 [24-92]; 94% had adenocarcinoma and 60% >2 metastatic sites at ctDNA collection. In EGFRm pts (n=58), driver GAs were detected in 69% of samples (61/88; 58 of them ex19/21), in ALKr pts (n=36) in 44% (27/61), and in BRAFV600Em pts (n=12) in 68% (25/37). In samples from EGFRm ex19/21 pts treated with 1st/2nd generation (gen.) TKI (n=51), the T790M mutation was detected in 27%; in those from pts treated with osimertinib (n=15), the C797S rate was 13%. In ALKr pts treated with crizotinib (n=17), ≥1 ALK resistance mutations were found in 12% (1 G1269A+F1174L, 1 G1202R), after 2nd gen. (n=16) in 31% (3 G1202R, 1 D1203N+F1174C, 1 T1151R) and after lorlatinib (n=16) in 13% (2 G1202R). Other GAs were identified in 10% (5/49) of samples: PTEN, PIK3CA, Her2, MET. In samples from BRAFV600Em pts treated with TKI (n=24; 22 with dabrafenib-trametinib), a total of 46% molecular alterations were found at PD: 5 KRAS/NRAS, 3 CTNNB1, 2 PIK3CA, 1 CDKN2A.
Conclusions
ctDNA is feasible in pts with NSCLC harbouring EGFRm, ALKr, BRAFV600Em for detecting driver and resistance GAs at PD, providing clinical informative results for treatment selection at TKI failure in 22% of cases. Outcomes of the following therapies based on ctDNA will be presented at the congress.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
P. Lavaud: Non-Financial Interests, Institutional, Advisory Role: Astellas; Non-Financial Interests, Institutional, Advisory Role: AstraZeneca; Non-Financial Interests, Institutional, Advisory Role: Sanofi; Financial Interests, Institutional, Other: Ipsen; Financial Interests, Institutional, Other: Mundi Pharma; Financial Interests, Institutional, Other: Janssen; Financial Interests, Institutional, Other: Pfizer. C. Morris: Financial Interests, Personal and Institutional, Full or part-time Employment: Inivata. K. Howarth: Financial Interests, Personal and Institutional, Full or part-time Employment: Inivata. D. Planchard: Non-Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical research, other: AstraZeneca; Non-Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical research: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Role, Lectures, Clinical research: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical research: Daiichi Sankyo; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical research: Eli Lilly; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical research: Merck; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical research, other: Pfizer; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, other: prIME Oncology; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, other: Roche; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria: Celgene; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria: Peer CME; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical research, other: Novartis; Financial Interests, Institutional, Principal Investigator: Sanofi-Aventis; Financial Interests, Institutional, Principal Investigator: Taiho Pharma; Financial Interests, Institutional, Principal Investigator: Novocure; Financial Interests, Institutional, Principal Investigator: MedImmune. B. Besse: Financial Interests, Institutional, Sponsor/Funding: AbbVie; Financial Interests, Institutional, Sponsor/Funding: Amgen; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Institutional, Sponsor/Funding: Biogene; Financial Interests, Institutional, Sponsor/Funding: Blueprint Medicines; Financial Interests, Institutional, Sponsor/Funding: BMS; Financial Interests, Institutional, Sponsor/Funding: Celgene; Financial Interests, Institutional, Sponsor/Funding: Eli Lilly; Financial Interests, Institutional, Sponsor/Funding: GSK; Financial Interests, Institutional, Sponsor/Funding: Ignyta; Financial Interests, Institutional, Sponsor/Funding: Ipsen; Financial Interests, Institutional, Sponsor/Funding: Merck KGaA; Financial Interests, Institutional, Sponsor/Funding: MSD; Financial Interests, Institutional, Sponsor/Funding: Nektar; Financial Interests, Institutional, Sponsor/Funding: Onxeo; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: PharmaMar; Financial Interests, Institutional, Sponsor/Funding: Sanofi; Financial Interests, Institutional, Sponsor/Funding: Spectrum Pharmaceuticals; Financial Interests, Institutional, Sponsor/Funding: Takeda; Financial Interests, Institutional, Sponsor/Funding: Tiziana Pharma; Financial Interests, Institutional, Sponsor/Funding: Boehringer Ingelheim; Financial Interests, Institutional, Sponsor/Funding: Crystal Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Daiichi Sankyo; Financial Interests, Institutional, Sponsor/Funding: Inivata; Financial Interests, Institutional, Sponsor/Funding: Janssen; Financial Interests, Institutional, Sponsor/Funding: Roche-Genentech; Financial Interests, Institutional, Sponsor/Funding: Servier; Financial Interests, Institutional, Sponsor/Funding: Tolero Pharmaceuticals. L. Mezquita: Financial Interests, Institutional, Advisory Role, Lectures, other: Roche; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Tecnofarma; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Other: Chugai. All other authors have declared no conflicts of interest.