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Expert Point of View: Jonathan Ledermann, MD, and Clara MacKay


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Jonathan Ledermann, MD

Jonathan Ledermann, MD

“A KEY AIM of treatment is the need to focus on preventing recurrence, which happens in 70% of patients. Over the past 20 years, we have made few inroads in preventing recurrence. This study brings a poly (ADP-ribose) polymerase (PARP) inhibitor olaparib (Lynparza) to the first-line setting, evaluating its action in BRCA-positive ovarian cancer. PARP inhibitors are most active in these patients who are therefore the best group to test PARP inhibitors as first-line treatment,” noted Jonathan Ledermann, MD, Professor of Medical Oncology, UCL Cancer Institute, University College London.

“With a minimum of 3 years of follow-up, the data show robust progression-free survival after stopping the PARP inhibitor at 2 years. At this point, the survival curves are not coming together. This interesting result will need longer-term follow-up. However, the fact that median progression-free survival was not reached is very encouraging compared to results of trials of cytotoxic chemotherapy and bevacizumab [Avastin]. We haven’t seen this magnitude of benefit in the past,” Dr. Ledermann told listeners at a press conference held during the European Society for Medical Oncology (ESMO) 2018 Congress.

“The real hope is that this treatment will lead to an improved cure rate. There is no doubt that this is a big step forward for BRCA-positive advanced ovarian cancer. This is a landmark trial for patients with ovarian cancer,” Dr. Ledermann stated.

One of the challenges to overcome is the implementation of universal BRCA testing at the diagnosis of ovarian cancer, even in those without a family history, so that candidates for PARP inhibitor therapy can be identified early. Access to these high-cost drugs may be difficult in some countries, and overcoming this will be important, so that patients can benefit from this new treatment, Dr. Ledermann said.

Ongoing studies that will shed more light on maintenance therapy with a PARP inhibitor include PRIMA (niraparib [Zejula] maintenance in poor-prognosis advanced ovarian cancer after response to first-line platinum-based therapy) and PAOLA-1 (olaparib maintenance with bevacizumab in high-grade serous or endometrioid disease and after first-line platinum-based chemotherapy with bevacizumab maintenance). These studies include patients without a BRCA mutation.

Variations in BRCA Testing

Clara MacKay

Clara MacKay

THERE ARE WIDE geographic variations in the rate of testing for BRCA mutations. Current estimates in the United States are that about 80% of patients with ovarian cancer are tested, either pre-or postdiagnosis, explained Clara MacKay, Project Director for the World Ovarian Cancer Coalition, who was present at the ESMO press conference.

“There is an urgent need to ensure that women diagnosed with ovarian cancer have access to genetic testing and understand the significance of a strong family history. We need to do better to ensure that important breakthroughs are moved forward,” Ms. MacKay said.

The speed of receiving genetic test results is also important for selection of therapy, agreed Dr. Ledermann and Ms. MacKay. “Clinicians have reported that in the United States, it can take around 14 days, whereas in Australia it can be 3 to 4 months,” Ms. MacKay said. ■

DISCLOSURE: Dr. Ledermann has received honoraria from Roche and AstraZeneca/MedImmune; is a consultant/advisor with AstraZeneca/MedImmune, Clovis Oncology, Roche, and Pfizer; is a member of the speakers bureau for Pfizer and Clovis Oncology; and has received research funding from AstraZeneca. Ms. MacKay reported no conflicts of interest.


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TWO-YEAR MAINTENANCE therapy with olaparib (Lynparza), a poly (ADP-ribose) polymerase inhibitor, achieved a significant improvement in progression-free survival in patients with newly diagnosed advanced ovarian cancer and a BRCA1 or BRCA2 mutation, according to results of the phase III SOLO-1...

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