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Expert Point of View: Jonathan Ledermann, MD


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Jonathan Ledermann, MD, of UCL Cancer Institute University College London, was the formal discussant of both the phase III SOLO1 and PAOLA-1 trials. He was quite enthusiastic about SOLO1: “Perhaps, this is really cure we are seeing.” He also noted that overall survival is still immature and is needed to confirm these findings.

In SOLO1, the 7-year survival rates were not quite statistically significant, he noted. “However, 90% stopped PARP inhibitor at 2 years, and here we are looking at 7 years. Survival is sustained. This occurred in the face of a 44% crossover rate in the placebo group and is a big clinically meaningful difference,” Dr. Ledermann told the audience. 

Jonathan Ledermann, MD

Jonathan Ledermann, MD

“We have little to compare this with, because we don’t have historical switch trials,” he continued. “Most patients who recur will eventually succumb to their disease. Looking at patients who do not recur is important.”

“In the control arm, of PAOLA-1, there is a plateau. About 20% do not experience disease progression after chemotherapy. In the olaparib-plus-bevacizumab arm, only a handful of patients required subsequent treatment, suggesting a proportion of patients might be cured,” he continued.

“Not all BRCA-positive patients are the same. It will be important to determine why 55% of patients required further therapy,” he added.

The data from PAOLA-1 add to a body of evidence suggesting that bevacizumab may not provide added value to PARP inhibition alone, Dr. Ledermann noted. “What we can conclude [from both of these trials] is that these survival data confirm the value of biomarker-directed first-line therapy with maintenance PARP inhibitors—here with olaparib—in the treatment of ovarian cancer,” Dr. Ledermann stated. 

DISCLOSURE: Dr. Ledermann reported no conflicts of interest.

 


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