2207P - Mainstream germline genetic testing in routine oncological care of EGFR mutant non-small cell lung cancer in the United Kingdom

Background

The hereditary nature of non-small cell lung cancer (NSCLC) is poorly understood. Previous studies have found inherited pathogenic germline variants (PGVs) are more common in patients with EGFR mutant (EGFRm) NSCLC. We sought to describe the frequency of PGVs in a cohort of EGFRm patients undergoing treatment at a UK cancer centre.

Methods

We invited NSCLC patients with activating somatic mutations in exon 18-21 of EGFR who attended the Royal Marsden Hospital Lung Unit between May 2022 to April 2023 to participate in a pilot of mainstream germline genetic testing. Patients consented to germline testing with an 84 gene panel of known hereditary cancer-related genes. Demographic data, clinicopathological information and family history were recorded.

Results

To date, 49 patients have undergone germline genetic testing. The median age of diagnosis was 60 years, all had adenocarcinoma histology, 65% were female, 71% were never smokers and 18% had a family history of lung cancer (Table). The most frequent somatic EGFR mutations were exon 19 deletions and L858R present in 63% and 18%, respectively. PGVs were detected in 8% (4/49) of patients. Two patients had PGVs detected in genes associated with a potential predisposition to lung cancer, a 37-year-old female with a TP53 PGV and a 71-year-old male with PGVs in both ATM and CHEK2. The remaining two patients had PGVs in genes not yet known to be associated with an increased risk of lung cancer (MUTYH and MITF). Table: 2207P

Patient characteristics and genetic testing results

Conclusions

In a United Kingdom cohort of EGFRm NSCLC patients 2/49 (4%) had PGVs in lung cancer predisposing genes; the tumour suppressor gene TP53 and DNA damage repair pathway genes ATM and CHEK2. Our data support the feasibility and importance of germline testing in routine oncological care. Germline results should be considered as a risk criterion for inclusion in lung cancer CT screening programmes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The Royal Marsden Hospital.

Funding

Royal Marsden Partners.

Disclosure

H.M. O'Sullivan: Financial Interests, Personal, Invited Speaker: Amgen; Other, Conference Travel Expenses: Takeda. C. Milner-Watts: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca. A.R. Minchom: Financial Interests, Personal, Other, Expenses: Amgen pharmaceuticals, Loxo Oncology; Financial Interests, Personal, Invited Speaker: Bayer Pharmaceuticals, Chugai Pharmaceuticals, GSK, Janssen Pharmaceuticals, Merck pharmaceuticals; Financial Interests, Personal, Advisory Board: Faron pharmaceuticals, GSK, Janssen Pharmaceuticals, Merck pharmaceuticals, Takeda, Genmab; Financial Interests, Institutional, Other, Research funding: MSD, Merck Pharmaceuticals; Financial Interests, Personal, Other, Honoraria: Novartis Oncology. A. George: Financial Interests, Personal, Advisory Board, Advisory board attendance: AstraZeneca; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Other, Editorial and research review: Roche. S. Popat: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, BMS, Blueprint, Merck Serono, Guardant Health, BeiGene, Takeda, Lilly, Roche, Turning Point Therapeutics, GSK, MSD, Pfizer, Sanofi, EQRx; Financial Interests, Personal, Invited Speaker: Medscape, VJ Oncology; Financial Interests, Personal, Other, Journal Deputy Editor, Lung Cancer: Elsevier; Financial Interests, Institutional, Other, Sub-investigator: Amgen; Financial Interests, Institutional, Coordinating PI: Ariad, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Takeda, Turning Point Therapeutics, Roche, Janssen, BMS, Lilly; Financial Interests, Institutional, Local PI: AstraZeneca, Roche, GSK, Trizel; Financial Interests, Institutional, Other, Sub-Investigator: MSD, Blueprint; Financial Interests, Institutional, Research Grant: Guardant Health; Non-Financial Interests, Leadership Role, Chair of Steering Committee, Unpaid: British Thoracic Oncology Group; Non-Financial Interests, Officer, Thoracic Faculty, Unpaid: European Society of Medical Oncology; Non-Financial Interests, Leadership Role, Foundation Council Member, Unpaid: European Thoracic Oncology Platform; Non-Financial Interests, Advisory Role, Mesothelioma Task-force Member, Unpaid: International Association for the Study of Lung Cancer; Non-Financial Interests, Member of Board of Directors, Unpaid: Mesothelioma Applied Research Foundation; Non-Financial Interests, Advisory Role, Honorary Clinical Advisor, Unpaid: ALK Positive UK; Non-Financial Interests, Advisory Role, Research Advisory Group Member, Unpaid: Ruth Strauss Foundation; Non-Financial Interests, Advisory Role, Scientific Adivsory Board Member, Unpaid: Lung Cancer Europe. All other authors have declared no conflicts of interest.