Off-label use of olaparib in uncommon tumor locations in patients with impaired homologous recombination genes

Abstract

Objective: To describe the effectiveness and safety of olaparib off-label indications in patients with impaired homologous recombination genes and solid tumors different than those authorized.

Methods: A single-center, observational and retrospective study including patients treated with olaparib for off-label use. The main variables were patient characteristics, prior therapies, response to therapy, progression-free survival, overall survival and adverse events.

Results: A total of 6 patients were included. All patients had metastases and received 3 or more lines of prior treatment. The primary tumor locations and mutations were partner and localizer of BRCA2 (PALB2) intrahepatic cholangiocarcinoma, ataxia telangiectasia mutated (ATM) non-small cell lung adenocarcinoma, somatic breast cancer gene (sBRCA2) colorectal cancer, germinal breast cancer gene 2 (gBRCA2) breast neuroendocrine tumor, gBRCA2 ampullary cancer and gBRCA2 pancreatic neuroendocrine tumor. At the end of the study, one patient was still receiving olaparib showing more than 25 months of sustained stable disease response. No novel toxicities were observed besides those included in the product information.

Conclusions: There is limited published evidence on the use of olaparib in patients harboring pathogenic variants other than breast cancer genes, like PALB2 and ATM and conditions different than those authorized such as digestive tract, neuroendocrine and lung tumors. Further research is to assess the efficacy of olaparib in these patients.

Keywords: BRCA mutations; Deficiencia en recombinación homóloga; Digestive system neoplasms; Homologous recombination deficiency; Mutaciones BRCA; Neoplasias del tracto gastrointestinal; Neuroendocrine tumors; Off-label use; Olaparib; Tumores neuroendocrinos; Uso off-label.