Expert Point of View: Sandro Pignata, MD

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This study represents a significant step forward in the treatment of recurrent ovarian cancer. For exceptional responders, the natural history of the disease has changed.
— Sandro Pignata, MD

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“This study represents a significant step forward in the treatment of recurrent ovarian cancer,” stated formal discussant Sandro Pignata, MD, of the IRCCS National Cancer Institute “Fondazione G. Pascale,” Naples, Italy.

He highlighted some key factors: Patients selected for the study were those who responded to platinum-based chemotherapy, and the study included both germline BRCA–mutated and germline BRCA–nonmutated patients. Also, the study attempted to identify patients with homologous recombination deficiency using a test developed by Myriad Genetics.

“In the germline BRCA–mutated patients, we see more than a 15-month gain in progression-free survival. “These extraordinary results modify the clinical history of these patients. And for the first time, we see a significant effect of PARP (poly ADP-ribose polymerase) inhibition in nongermline BRCA–mutated patients. We also saw a benefit regardless of homologous recombination deficiency–positive status, and all wild-type BRCA patients benefited as well,” Dr. Pignata said.

Modifying Patient Selection

“These extraordinary results will modify the way we use PARP and include patients with nongermline BRCA mutations. Results show that the homologous recombination deficiency test can identify nonmutated patients likely to respond to therapy,” he added.

“It will be important how to select patients for PARP therapy. Sixty percent of these patients had a platinum-free interval of more than 1 year, and 51% were complete responders. These patients are highly sensitive to platinum. About 30% had more than three previous lines of therapy. Response to platinum is the key clinical parameter for selection of patients for niraparib,” he stated.

He emphasized that all patients who responded to platinum may benefit from niraparib: homologous recombination deficiency–positive BRCA wildtype, homologous recombination deficiency–negative, germline BRCA–mutated, and nongermline BRCA–mutated.

Homologous Recombination Deficiency Testing

Dr. Pignata said it is possible that the Myriad Genetics test for homologous recombination deficiency may not have been completely accurate, perhaps mislabeling some homologous recombination deficiency–positive cases as homologous recombination deficiency–negative. It is also possible, he continued, that homologous recombination deficiency–positive tumors are more frequent than previously assumed.

Because the test is not 100% specific, and the heterogeneity of the disease evolves over time, “the test performed at the time of enrollment in a trial may not represent the patient as she enters the trial,” he further explained. These are two different time points: enrollment and then treatment. “A better test is needed,” he suggested.

Identifying Responders

“There were lots of exceptional responders. Who are these patients? We can’t identify them by BRCA and homologous recombination deficiency testing. For exceptional responders, the natural history of the disease has changed. We have never seen responses like this before,” Dr. Pignata stated. ■

Disclosure: Dr. Pignata has received honoraria from Roche and AstraZeneca.

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