Dr. O'Reilly on Investigational Treatment Approaches in Pancreatic Cancer

Eileen O'Reilly, MD, Winthrop Rockefeller Endowed Chair in Medical Oncology, co-director, Medical Initiatives, David M. Rubenstein Center for Pancreatic Cancer Research, section head, Hepatopancreaticobilary and Neuroendocrine Cancers, and medical oncologist, Memorial Sloan Kettering Cancer Center, discusses investigational treatment approaches in advanced pancreatic cancer.

There is ongoing research examining stromal modulation DNA repair and broadening its utility to patients with other homologous repair gene mutations, says O’Reilly. However, whether the signal with olaparib (Lynparza) applies to patients with PALB2, somatic BRCA, ATM, mcm5-bob1, or NBN mutations is still being investigated, as these are rare alterations.

Olaparib (Lynparza) has shown single-agent activity in patients with BRCA-mutant disease. Therefore, exploring PARP inhibitors in combination with other agents could extend their utility. Such was the case in ovarian cancer, where maintenance therapy with the combination of olaparib and bevacizumab (Avastin) led to an improvement in progression-free survival versus bevacizumab and placebo in patients with newly diagnosed advanced disease. However, VEGF-targeted strategies have not, for the most part, shown value in pancreatic cancer, says O’Reilly.

Immunotherapy has also been an elusive strategy in pancreatic cancer, adds O’Reilly. However, combinations of chemotherapy and immunotherapy, which are being evaluated in the frontline and second-line settings, are expected to read out over the next year. Additional immune-modulating agents, such as CD40-directed drugs, could be another path forward, concludes O’Reilly.