Abstract 1482P
Background
Compelling evidence suggests that up to 15% of PC may be due to germline Pathogenic Variants (PV) in high-risk genes. Because of this, international guidelines recommend multigene germline testing for all PC patients. However, the precise contribution of additional susceptibility genes other than BRCA is still to be clarified, as different panel were used among different studies.
Methods
We aimed to evaluate the prevalence of PVs in DNA Damage Repair (DDR) and other candidate susceptibility genes through an oncologist-led Multiple Gene Panel (MGP) testing in a retrospective series of unselected PC patients treated at our cancer center. We investigated the impact of these PVs on outcomes. The germline MGP tested 53 genes, selected according to the recent literature. Only PVs and Likely Pathogenetic Variants (LPVs) were included in the analyses. Student’s t-test, chi square and log-rank test were used to test the association with age, stage and Overall Survival (OS), respectively.
Results
A total of 185 patients were included in the analyses. We found either a PV or LPV in 43/185 patients (23.2%), with PVs in 17.3% and LPVs in 7% of the patients. A BRCA1/2 PV or LPV was found in 8/185 patients (4.3%). The most frequent altered genes other than BRCA were CDKN2A (3.7%), CHEK2 and ATM (2.7%), COL7A1 (4.8%). Median age (56 yrs overall, range 14-84) and stage IV frequency at diagnosis did not differ in Wild-Type (WT) and PV+LPV patients. Median OS (mOS) was 11 months. A trend towards better survival was observed among PV+LPV (12.9 mOS) than among WT cases (9.4 mOS), although not statistically significant (p=0.17). Among the 17 patients who survived for longer than 20 months, there were one COL7A1 LPV, 2 CDKN2A and 2 ATM PV carriers, one of whom is still alive at 57 months from diagnosis and start of neoadiuvant gemcitabine-abraxane chemotherapy. Few data available about chemotherapy regimens do not allow further analyses.
Conclusions
A high PV and LPV overall frequency was found (23%), with a 4.3% of BRCA PV rate, in line with the literature. Interestingly, we found a 3.5 month longer mOS in PV+LPV as compared to WT patients, although not statistically significant. Encouraging good prognosis was observed for some ‘outliers’ with PVs and LPVs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
LILT.
Disclosure
S. Sciallero: Non-Financial Interests, Personal and Institutional, Invited Speaker: Amgen; Non-Financial Interests, Personal and Institutional, Invited Speaker: Servier; Non-Financial Interests, Personal and Institutional, Invited Speaker: Merck; Non-Financial Interests, Personal, Other, Participation at congresses: Novartis; Non-Financial Interests, Personal, Other, Participation at congresses: Ipsen. All other authors have declared no conflicts of interest.