Bradley J. Monk, MD: The other question is, why don’t you use both? Why don’t you use bevacizumab [Avastin] and PARP inhibition together? We had that published in the New England Journal of Medicine, and the approval is in process. Sharyn, tell us about the study that we call PAOLA-1. There’s a 1 after it just like SOLO-1, because it’s a first-line study. Go ahead.
Sharyn N. Lewin, MD: PAOLA-1 was 1 of the groundbreaking discussions that started at ESMO [European Society for Medical Oncology Congress]. This was a trial that enrolled women with stage III and stage IV epithelial ovarian cancer. Patients were enrolled regardless of surgical outcome, which was a little different from PRIMA. Women who were eligible for the study all had to have either a CR [complete response] or a PR [partial response] following carboplatin, paclitaxel, and bevacizumab therapy. This was a European trial. It was enrolled throughout 8 different countries. Bevacizumab was utilized in the frontline setting with chemotherapy and then as maintenance. These women were then randomized, if they had a CR or PR, to either bevacizumab alone or olaparib and bevacizumab. The bevacizumab arm was continued for 15 months and the olaparib was continued for up to 24 months, or until there was some type of unacceptable toxicity or progression.
The primary end point on this study was time from randomization until investigator-assessed disease progression or death. Certain subgroup analyses included PFS [progression-free survival] by BICR [blinded independent central review] and PFS2 [progression after the next line of therapy]. There are also secondary end points, and tumor was analyzed for HRD [homologous recombination deficiency] via myChoice CDx. In total, over 800 patients were enrolled. Baseline characteristics were well balanced between the groups. It’s interesting that about 30% of patients had stage IV disease. Most of the patients were actually NED [no evidence of disease], going to either a complete cytoreduction or having a CR after frontline therapy. It was very interesting.
The duration of investigator-assessed PFS was significantly longer in the olaparib and bevacizumab arm than in the bevacizumab alone arm, with a median of 22 months versus 16.6 months. That led to a hazard ratio of 0.59. There was essentially a 41% risk reduction of progression or death if receiving the combination of olaparib and bevacizumab versus bevacizumab alone.
Looking at the various subgroups, for patients who had HRD-positive BRCA-mutated tumors, median PFS was amazingly 37 months with the combination of olaparib and bevacizumab versus only 17 months in the bevacizumab-alone arm. That was a hazard ration of 0.33. If you’re looking at patients who had HRD positivity without a tissue BRCA mutation, the median PFS was 28 months in the combination arm versus 16 months in the Avastin-alone arm. That was a hazard ratio of 0.47. Interestingly enough, in the patients who were negative for HRD or had an unknown status, we saw that the median PFS was the same between the 2 groups: 16 months in both arms, and the hazard ratio was 0.92.
We did not see any new safety signals. As I mentioned, the trial did meet its primary end point. It was very impressive to see the response of the 2 drugs together—bevacizumab and olaparib—in these patients.
Transcript edited for clarity.