Abstract 52P
Background
Fusions in the ROS1 proto-oncogene are among the best treatable genetic aberrations in Non-small cell lung cancer (NSCLC). Besides the occurrence of solvent-front mutations (SFM) in acquired resistance to targeted therapy, little is known about ROS1 aberrations other than fusions. We analyzed molecular and clinical characteristics of ROS1 mutations in NSCLC patients without activating ROS1 fusions or SFMs.
Methods
Next-generation sequencing (NGS) was performed on tissue samples from NSCLC patients within the National Network Genomic Medicine (nNGM). Patients with activating ROS1 fusions detected by fluorescence in-situ hybridization (FISH) were excluded. We analyzed the mutations’ frequencies and characteristics as well as co-occurring mutations.
Results
Of 8072 patients analyzed by NGS between 2018 and 2021, 118 (1.5%) patients harbored ROS1 mutations. Most patients were male (76.3%) and had adenocarcinoma histology (57.6%). The median age at diagnosis amounted to 68 years. Nearly all of the patients (96.5%) had a smoking history, amassing 40 pack-years on average. The most frequent ROS1 mutations were transversions (53.6%), without defining a genomic hotspot region. Besides TP53 mutations (61.0%), KRAS (25.4%), EGFR (7.6%), PIK3CA and FGFR1-4 mutations (5.9% each) co-occurred most frequently. In 12 (10.2%) patients, ROS1 mutation was the only detected aberration.
Conclusions
Our cohort opposites the clinical characteristics of patients with ROS1 fusion regarding sex, smoking history, age, and histology. Further research is warranted to characterize their biological impact and their potential to act as a drug target.
Legal entity responsible for the study
Matthias Scheffler.
Funding
Has not received any funding.
Disclosure
S. Michels: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Janssen Pharmaceuticals. L. Nogova: Financial Interests, Personal, Invited Speaker, Consultant: Pfizer; Financial Interests, Personal, Invited Speaker: Celegene; Financial Interests, Personal, Invited Speaker, Consultant: Novartis; Financial Interests, Personal, Invited Speaker, Consultant: Roche; Financial Interests, Personal, Invited Speaker, Consultant: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker, Consultant: Janssen Pharmaceuticals; Financial Interests, Personal, Invited Speaker, Consultant: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker, Consultant: MSD. D. Schaufler: Financial Interests, Personal, Other: Bristol Myers Squibb; Financial Interests, Personal, Other: Boehringer-Ingelheim; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other, honoraria: Roche; Financial Interests, Personal, Other: AbbVie; Financial Interests, Personal, Other: Loxo Oncology; Financial Interests, Institutional, Other: Pfizer; Financial Interests, Institutional, Other: Bristol Myers Squibb; Financial Interests, Institutional, Other: Novartis; Financial Interests, Institutional, Other: MSD; Financial Interests, Institutional, Other: Janssen Pharmaceuticals; Financial Interests, Personal, Other: AstraZeneca. R. Fischer: Financial Interests, Personal, Other, honoraria, ResearchFunding, Advisory Role/Expert Testimony: Bristol Myers Squibb; Financial Interests, Personal, Other, honoraria, ResearchFunding: MSD; Financial Interests, Personal, Other, honoraria, advisory role/Expert Testimony: Roche; Financial Interests, Personal, Other, honoraria: Boehringer-Ingelheim; Financial Interests, Personal, Other, honoraria: Astra Zeneca. R. Riedel: Financial Interests, Personal, Other, honoraria, travel funding: Boehringer-Ingelheim; Financial Interests, Personal, Other, honoraria, travel funding: Novartis; Financial Interests, Personal, Other, travel funding: Loxo Oncology; Financial Interests, Personal, Other, travel funding: Lilly; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Janssen Pharmaceuticals. S. Merkelbach-Bruse: Financial Interests, Personal, Other, personal fee and honoraria: Astra Zeneca; Financial Interests, Personal, Other, personal fee and honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, personal fee and honoraria: Novartis; Financial Interests, Personal, Other, personal fee and honoraria: Roche; Financial Interests, Personal, Other, personal fee and honoraria: Bayer; Financial Interests, Personal, Other, personal fee and honoraria: Pfizer. R. Büttner: Financial Interests, Personal, Other, Consultant: Pfizer; Financial Interests, Personal, Other, Consultant: Novartis; Financial Interests, Personal, Leadership Role, CSO: Targos Molecular Pathology. J. Wolf: Financial Interests, Personal, Other, honoraria, consultant, travel funding: AbbVie; Financial Interests, Personal, Other, honoraria, consultant, travel funding: Astra Zeneca; Financial Interests, Personal, Other, honoraria, consultant, travel funding: Bristol Myers Squibb; Financial Interests, Personal, Other, honoraria, consultant, travel funding: Boehringer-Ingelheim; Financial Interests, Personal, Other, honoraria, consultant, travel funding: Chugai; Financial Interests, Personal, Other, honoraria, consultant, travel funding: Ignyta; Financial Interests, Personal, Other, honoraria, consultant, travel funding: Lilly; Financial Interests, Personal, Other, honoraria, consultant, travel funding: MSD; Financial Interests, Personal, Other, honoraria, consultant, travel funding: Novartis; Financial Interests, Personal, Other, honoraria, consultant, travel funding: Pfizer; Financial Interests, Personal, Other, honoraria, consultant, travel funding: Roche; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Janssen Pharmaceuticals. M. Scheffler: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Other, consultant: Bristol Myers Squibb; Financial Interests, Personal, Other, consultant, travel funding: Boehringer-Ingelheim; Financial Interests, Personal, Other, consultant: Takeda; Financial Interests, Personal, Other, consultant: Roche; Financial Interests, Personal, Other, travel funding: Mediolanum; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Janssen Pharmaceuticals. All other authors have declared no conflicts of interest.