178P Germline testing in non-small cell lung cancer (NSCLC): Real-world impact of the discovery of germline pathogenic variants (PGV) in the INHERITY LC (ILC) study

It is estimated that around 8% of NSCLC are linked to genetic predisposition. However, there is no criteria for study on Genetic Counseling Units (GCU). In the ILC study we identified 11% of PGVs in patients (pts) with NSCLC. Here, we report the real-world impact of the discovery of PGVs in pts with NSCLC and their families. The ILC study is a multicentric prospective study of 148 pts with NSCLC with germline testing performed by NGS (Spain). This is a substudy of 16 pts harboring PGVs in cancer predisposition genes. Clinical and molecular data of the tumors, GCUs study, genetic counseling recommendations for pts/families and their results were collected from medical reports. Out of 148 pts enrolled, we identified PGVs in 16 (11%) involving CHEK2 (3/19%), NBN (3), ATM (2/13%), BARD1 (1/6%), BRCA2 (1), FAN1 (1), MLH1 (1), MRE11 (1), PALB2 (1), TP53 (1), XRCC2 (1). In PGV-carriers, median age was 60 years (31-79), 63% were female and 69% smokers; 69% had advanced disease, mainly adenocarcinoma histology (69%) and 56% with a somatic driver alteration. Of the 16 PGV-carriers, 14 cases (88%) did not met criteria for genetic testing. After the ILC results, 13 were derived to a GCU. In 7 pts (44%) cancer screening for solid tumors has been initiated while in 6 (37%) was not initiated because of death for cancer progression. In 1 patient with an EGFR mutated lung adenocarcinoma harboring a PGV in MLH1, a prophylactic hysterectomy was performed. We identified 6 pts with PGV with potential therapeutic implications in genes involved in DNA (4/25%) and mismatch repair (1/6%). Regarding the family impact, in 10 families (63%) cascade study was recommended performing germline testing in 27 healthy relatives. Of them, in 12 individuals a PGV was detected in BRCA2, CHEK2, FAN1, MLH1, MRE11, NBN, TP53 and XRCC2. All of them are current under follow-up by GCU for preventive measures. In this real-world cohort, most of the carriers identified did not met criteria for genetic testing according to the current guidelines. However, the discovery of PGVs in NSCLC led to assessment and follow-up by GCU for both pts and their relatives for cancer screening. Specific criteria for genetic testing in NSCLC are needed.