Abstract 357P
Background
DDR pathway has been introduced as a new target of treatment in solid cancers, through the exploitation of synthetic lethality. The aim of this study is to evaluate the incidence of GM in DDR genes in aPDAC pts and to establish their prognostic and predictive role and their family implications.
Methods
Pts received a 26-genes sequencing by Sophia Genetics’ multigenic panel; when the panel could not be performed only BRCA 1/2 genes were analyzed by PCR. According to test results, pts were divided into 3 groups: pts with pathogenic variants (PVs), pts with variants of uncertain significance (VUS) and pts with no alterations. Primary endpoints were progression-free survival (PFS) and overall survival (OS). The Kaplan–Meier method was used to estimate efficacy outcome; log-rank test and Cox-regression model were used to compare the differences, considering a statistically significant p value < 0.05.
Results
From September 2019 to August 2023, 214 pts were enrolled; 154 (72%) pts received the entire panel and 64 (28%) pts were evaluated only for BRCA 1/2. BRCA 1/2 PVs were found in 13 pts (6%), VUS were found in 19 pts (8.9%) and 182 pts (85.1%) were BRCA wt. Among 154 pts tested with the entire panel, 20 (13%) pts had a PV of one of the other 24 genes, 39 (25.3%) had a VUS and 95 (61.7%) had no GMs; the genes with PVs were: 9 (5.8%) ATM, 7 (4.5%) MUTYH, 1 (0.6%) BARD1, 1 (0.6%) PALB2, 1 (0.6%) XRCC2, 1 (0.6%) NBN. A statistically significant association emerged between cancer family history and DDR genes’ alterations: 77% in PVs pts, 82% in VUS pts and 59% in pts with no GMs; p 0.005. First-line therapy mPFS was 7.8 months (CI 95% 6.7-8.8) and mOS was 14.6 (CI 95% 12.7-17). A statistically significant difference in mOS was observed between the 3 groups: PVs pts 19.5 mos (CI 95% 14.5-not reached), VUS pts 13.4 mos (CI 95% 10-19.9), pts with no GMs 14.6 mos (CI 95% 12.5-17.5), p=0.017. Platinum-based treatment was not associated neither with PFS nor OS in any of the 3 groups.
Conclusions
Our data show a high incidence rate of DDR genes’ GM and confirm the importance of genetic testing in all PDAC pts, due to the therapeutic implications and cancer risk prevention in patients’ relatives. The prognostic role of DDR GMs and the impact of VUS remain unclear.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.