Patients with biliary tract cancers such as cholangiocarcinoma (CCA) who have the BRCAness phenotype have better progression-free survival after exposure to platinum-based chemotherapy, according to a new study published in the European Journal of Cancer.

In addition, the trends of overall survival curves suggest that BRCAness patients “could benefit from a maintenance therapy with PARPi,” the authors said.

To investigate the effect of BRCAness in terms of disease prognosis in biliary tract cancers, a team of researchers led by Andrea Casadei-Gardini, MD, from the School of Medicine, Vita-Salute San Raffaele University in Milan, Italy analyzed tissue samples obtained from 150 patients with biliary tract cancers treated with platinum-based chemotherapy.


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Of these 150 patients, almost half (48%) had the BRCAness phenotype. The most commonly mutated genes in these patients were ARID1A, CDKN2A, KRAS/NRAS, CDKN2B, BRCA2, PBRM1, ATM, FGFR2, TP53, IRS2, and CREBBP.

Read more about the prognosis of CCA

Statistical analyses showed that BRCAness mutation was associated with longer median progression-free survival but not longer median overall survival in these patients though there was “a benefit in survival.”

Moreover, patients with a BRCAness mutation had a higher percentage of disease control rate. Statistical analyses confirmed BRCAness mutation to be an independent favorable prognostic factor for progression-free survival and there was a positive trend for overall survival.

In the future, sequential strategies based on treatments with platinum-based chemotherapy and PARP inhibitors should be tested, the researchers said.

BRCAness is defined as the set of traits where BRCA1 dysfunction caused by a mutation or methylation defects leads to a deficiency in DNA repair.

CCA is a group of rare malignant tumors originating from cells of the biliary tree. It is responsible for around 15% of all primary liver tumors and is the second most common primary liver malignancy after hepatocellular carcinoma.

Reference

Rimini M, Macarulla T, Burgio V, et al. Gene mutational profile of BRCAness and clinical implication in predicting response to platinum-based chemotherapy in patients with intrahepatic cholangiocarcinoma. Eur J Cancer. 2022;171:232-241. doi:10.1016/j.ejca.2022.05.004