Abstract 191P
Background
ROS1 fusion is a relatively low prevalence (1–2%) but targetable driver in non-small cell carcinoma (NSCLC). Therefore, robust and low-cost tests are desirable in order to identify patients harboring this fusion. ROS1 immunohistochemistry (IHC) using monoclonal antibody clone D4D6 is widely used for screening patients for a potential ROS1 fusion. However, due to relatively low specificity, confirmation using an orthogonal test (FISH or NGS) has been reported as necessary. We investigated the performance of a novel IHC clone SP384 in a retrospective, stage I-III, lung ADC cohort.
Methods
FFPE sections of resected ADC from the ETOP Lungscape multicenter cohort, constructed in tissue microarrays, were prospectively stained for ROS1 protein expression using the SP384 clone in a ready-to-use kit and Ventana immunostainers. After passing an external quality control, scoring was performed locally by trained pathologists using the H-score. Staining intensity of 2+ (any %) was considered IHC positive (IHC 2/3+). Subsequently, IHC 2/3+ cases were 1:1:1 matched with IHC 0/1+ cases, and subjected to FISH and NGS analyses.
Results
Valid immunostaining results were available in 866 pts with 35 (4%) IHC 2/3. Nineteen had an average H-score of <100, eleven of 100–199 and five of 200–300. Seven IHC 2/3+ cases were not further tested (5 with an EGFR mutation (1 with H-score >200), 1 with an ALK fusion, and 1 with no material left). Of the remaining 28 IHC 2/3+ cases, only 2 (50% of 4 tested with H-score ≥200) were confirmed to have a ROS1 rearrangement, leading to an overall prevalence of 0.23%. Of the ROS1 IHC 2/3+ cases not confirmed by FISH or NGS, 7 harbored a KRAS mutation and 1 a MET mutation. All matched IHC 0/1+ cases were negative by FISH/NGS. Thus, ROS1 positivity and negativity by FISH-NGS were correctly predicted 100% by IHC 2/3+, and 96% by IHC 0/1+, respectively.
Conclusions
The prevalence of ROS1 fusion in an ADC cohort screened by IHC using SP384 clone was relatively low compared to literature. No additional ROS1 fusion was identified by FISH or NGS among IHC 0/1+. Thus, this method is useful for preselection of patients with a potential ROS1 fusion, followed by confirmatory FISH and/or NGS.
Legal entity responsible for the study
ETOP IBCSG Partners Foundation.
Funding
Pfizer.
Disclosure
E.M. Speel: Financial Interests, Personal, Research Grant: AstraZeneca, Bayer, Pfizer. T. Radonic: Financial Interests, Institutional, Advisory Board, Advisory board RET fusions: Roche. U. Dafni: Financial Interests, Personal, Other, Member of the Tumor Agnostic Evidence Generation working Group: Roche. K.M. Kerr: Financial Interests, Personal, Advisory Board, Consultancy: AbbVie, Amgen, AstraZeneca, Bayer, Debiopharm, Diaceutics, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Roche Diagnostics/Ventana, Janssen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Roche Diagnostics/Ventana, Medscape, Prime Oncology; Non-Financial Interests, Personal, Leadership Role, Past Pathology Committee Chair: IASLC; Non-Financial Interests, Personal, Member, Lobbying and pressure group for UK - generally writing reports to lobby government: UK Lung Cancer Consortium. L. Bubendorf: Financial Interests, Personal, Advisory Board: Roche/Ventana, AstraZeneca, Pfizer, Thermo Fisher, Bayer, Takeda, Janssen. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GlaxoSmithKline, Gilead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, BMS, AstraZeneca, OncologyEducation, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology: Elsevier; Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS; Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: BeiGene; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Invited Speaker, LAGOON: Pharma Mar; Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Personal, Officer, ESMO President 2020–2022: ESMO; Non-Financial Interests, Personal, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP/EORTC/SAKK; Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), ASCO, AACR, IASLC; Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Leadership Role, Vice -President: SAMO; Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. R.A. Stahel: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Blueprint, Boehringer Ingelheim, GSK, MSD, Novartis, Roche, BMS; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Janssen, MSD, Pfizer, Roche, Sandoz, Seattle Genetics, Takeda, Boehringer Ingelheim, GSK; Financial Interests, Personal, Other, DMC: Takeda; Financial Interests, Personal, Other, Editor in Chief: Lung Cancer; Financial Interests, Personal, Other, Editor: CTR; Financial Interests, Institutional, Research Grant, ETOP study: Roche, AstraZeneca, BMS, MSD, Pfizer, Mirati, Janssen; Financial Interests, Institutional, Research Grant, IBCSG study: Novartis, Ipsen, Pierre Fabre, MSD, Pfizer, Roche, AstraZeneca, Celgene; Non-Financial Interests, Personal, Invited Speaker, President Foundation Council: IBCSG, ETOP. All other authors have declared no conflicts of interest.