Clinical outcomes and response to chemotherapy in a cohort of pancreatic cancer patients with germline variants of unknown significance (VUS) in BRCA1 and BRCA2 genes.

Abstract

The clinical outcome and the efficacy of chemotherapy in pancreatic cancer patients with BRCA1/2 Variants of Unknown Significance (VUS) is unknown. We explored the effects of chemotherapy with or without Platinum in non metastatic and metastatic pancreatic cancer patients with BRCA1/2 VUS. A retrospective analysis of non-metastatic or metastatic pancreatic cancer patients with gBRCA1/2 VUS treated in 13 Italian centers between November 2015 and December 2020 was performed. All patients were assessed for toxicity and RECIST 1.1 response. Metastatic patients were evaluated for survival outcome. 30 pancreatic cancer patients with gBRCA1/2 VUS were considered: 20 were M+ and 10 were non-M+. Pl-CT was recommended to 16 patients: 10 M+ (6 FOLFIRINOX and 4 PAXG) and 6 non-M+ (3 FOLFIRINOX and 3 PAXG); 11 patients received Nabpaclitaxel-Gemcitabine (AG; 8 M+) and 3 patients (2 M+) were treated with Gemcitabine (G). The RECIST 1.1 response rate was 27% for AG and 44% for Pl-CT (22% for (m) FOLFIRINOX and 71% PAXG). 1year Progression-Free Survival was 37.5% for patients treated with AG and 33% in the Pl-CT subgroup. Median Overall Survival (OS) was 23.5months for patients treated with AG and 14months for the Pl-CT subgroup. 1Year and 2Year OS were numerically better for AG (1Year OS: 75% vs 60% and 2Year OS: 50% and 20% in AG and Pl-CT subgroups, respectively) as well. Pl-CT does not seem to be associated with a better outcome compared to AG chemotherapy in PDAC patients with BRCA 1/2 VUS.