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

Cancer Chemother Pharmacol. 2023 Dec;92(6):501-510. doi: 10.1007/s00280-023-04585-w. Epub 2023 Sep 19.

Abstract

Purpose: 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.

Methods: 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.

Results: 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). 1 year Progression-Free Survival was 37.5% for patients treated with AG and 33% in the Pl-CT subgroup. Median Overall Survival (OS) was 23.5 months for patients treated with AG and 14 months for the Pl-CT subgroup. 1 Year and 2 Year OS were numerically better for AG (1 Year OS: 75% vs 60% and 2 Year OS: 50% and 20% in AG and Pl-CT subgroups, respectively) as well.

Conclusions: Pl-CT does not seem to be associated with a better outcome compared to AG chemotherapy in PDAC patients with BRCA 1/2 VUS.

Keywords: BRCA Variants of Unknown Significance (VUS); Chemotherapy response; Chemotherapy toxicity; Pancreatic cancer; Platinum chemotherapy.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Genes, BRCA2
  • Humans
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / pathology
  • Retrospective Studies

Substances

  • BRCA1 protein, human
  • BRCA1 Protein
  • BRCA2 protein, human
  • BRCA2 Protein