Durable Response after Olaparib Treatment for Perihilar Cholangiocarcinoma with Germline BRCA2 Mutation

Despite major advances in surveillance and management, advanced cholangiocarcinoma (CCA) still carries a dismal prognosis. In recent years, several actionable genomic alterations in pancreatobiliary malignancies have been identified. For instance, homologous recombination deficiency (HRD) has been considered a predictive biomarker of clinical response to platinum and poly (ADP-ribose) polymerase (PARP) inhibitors.

A 53-year-old man with a stage 3 (T4N0M0) BRCA2-mutant CCA developed intolerable toxicity after 44 cycles of gemcitabine/cisplatin. In light of his HRD positivity, treatment was switched to single-agent olaparib. The patient showed a partial radiological response, which was maintained after 8 months of olaparib discontinuation (progression-free survival >36 months).

Given the durable response observed, olaparib can be a valuable therapeutic tool in BRCA-mutant CCAs. Ongoing and future clinical trials are needed to confirm the role of PARP inhibition in similar patients and to define the clinicopathological and molecular profile of the individuals most likely to benefit.