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PARP Inhibitor Effective in Advanced Pancreatic Cancer

Pancreatic cancer.

Poly (ADP-ribose) polymerase (PARP) inhibitors, such as rucaparib (Rubraca®, Clovis Oncology), have been shown to be effective for cancers containing BRCA mutations. They have also been successful as maintenance therapy for platinum-sensitive ovarian cancer treated with PARP inhibitors. Therefore, researchers conducted a phase 2 clinical trial to determine if patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic BRCA or PALB2 mutation whose cancer had not progressed following at least four months of platinum-based chemotherapy would experience disease control with maintenance rucaparib monotherapy. Results revealed that rucaparib is a promising drug for these patients, who otherwise face a dismal prognosis.

For this study, presented at the American Association for Cancer Research Annual Meeting 2019, 42 patients with BRCA- or PALB2-mutated, platinum-sensitive, advanced pancreatic cancer with at least four months of prior platinum-based chemotherapy without evidence of disease progression were orally administered 600 mg rucaparib twice daily until disease progression or unacceptable toxicity. Patients enrolled in the study were predominately female, with a median age of 61 years.

Rucaparib was associated with a median progression-free survival of 9.1 months and an overall response rate of 36.8%. It was well tolerated, with the most common treatment-related adverse events being nausea, dysgeusia, and fatigue.

The study authors conclude, "Based on these early data, maintenance rucaparib following induction with platinum-based chemotherapy shows encouraging disease control with minimal toxicity in patients with platinum-sensitive advanced [pancreatic cancer] and a pathogenic mutation in BRCA1, BRCA2, or PALB2."

For More Information

Clinicaltrials.gov (2019). Maintenance rucaparib in BRCA1, BRCA2, or PALB2 mutated pancreatic cancer that has not progressed on platinum-based therapy. NLM identifier: NCT03140670.

Binder KAR, Mick R, O'Hara M, et al (2019). A phase II, single arm study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic mutation in BRAC1, BRCA2, or PALB2. American Association for Cancer Research Annual Meeting 2019. Abstract CT234. 

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