BRCA status is the strongest determinant of benefit from treatment with a PARP inhibitor and should be assessed in all patients with high-grade tumors.

— Jonathan Ledermann, MD

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Invited discussant Jonathan Ledermann, MD, of UCL Cancer Institute, University College London, said the ARIEL2 results for rucaparib (Rubraca) add to the evidence base for PARP (poly ADP-ribose polymerase) inhibition in ovarian cancer established by olaparib (Lynparza). It’s been about 2 years since the U.S. Food and Drug Administration approved olaparib as single-agent therapy for previously treated BRCA-mutant ovarian cancer. This was followed in 2016 by the approval of rucaparib for patients who received one or two prior therapies.

“There is a clear clinical benefit of olaparib or rucaparib in the treatment of BRCA-mutated recurrent, high-grade ovarian cancer,” Dr. Ledermann noted. “Single-agent activity correlates with the platinum-free interval and the number of prior lines of chemotherapy. BRCA status is the strongest determinant of benefit from treatment with a PARP inhibitor and should be assessed in all patients with high-grade tumors.”

“We know from experience with olaparib that there is a long-term benefit with maintenance therapy with a PARP inhibitor (as licensed by the European Medicines Agency and other regulatory organizations outside the United States), as 15% of patients remain progression-free for 5 years,” he continued. “Maintenance and single-agent strategies are both effective in the short term, and we will have to await results of the ARIEL3 and ­ARIEL4 trials with rucaparib to see whether long-term results are similar.”

ARIEL3 is evaluating rucaparib as maintenance therapy, postplatinum-based chemotherapy, and the randomized, phase III confirmatory ­ARIEL4 trial is comparing single-agent rucaparib with standard therapy in relapsed BRCA-mutated patients. ■

Disclosure: Dr. Ledermann reported no potential conflicts of interest.