Expert Point of View: Jonathan Ledermann, MD


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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

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.


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