Oliver Dorigo, MD, PhD: Olaparib was approved by the FDA for the treatment of patients with BRCA1- and BRCA2-mutated ovarian cancer. The approval was largely based on a study that enrolled patients who had 3 or more lines of prior chemotherapy for ovarian cancer. Those patients were BRCA1 and BRCA2 carriers. The study included other patients as well, those with breast cancer, pancreatic cancer, and prostate cancer. The overall response rate in this patient population was 31%.

Given that the patient population with ovarian cancer in this trial published by Kaufman a couple of years ago was highly platinum-resistant due to the many lines of chemotherapy prior, the 31% sent a very strong signal to all of us that this therapy in platinum-resistant patients is really meaningful. As a comparison, any patient with platinum-resistant ovarian cancer treated with standard chemotherapy has a response rate of about 15% to 20%. But 31% in the selective patient population of BRCA1 or BRCA2 mutation carriers was very exciting to us. That’s why the FDA approved olaparib for the treatment of patients with these indications: 3 or more prior lines of chemotherapy and germline BRCA1 or BRCA2 mutation carriers.

Whitney S. Graybill, MD, MS: Olaparib was recently approved in the maintenance setting for patients with platinum-sensitive recurrent ovarian cancer. This approval really came about as a result of 2 different clinical trials. Study 19 was a phase II trial that evaluated olaparib versus placebo in patients with platinum-sensitive recurrent disease. There was a significant increase in progression-free survival for patients who received olaparib as compared to placebo, 8.4 months versus 4.8 months.

Now, while patients were eligible for this trial regardless of BRCA status, the progression-free survival was significantly increased in patients who were BRCA-positive. The EMA approved olaparib in the maintenance setting based on the results of the study, but the FDA felt that there needed to be additional data, which is really how the SOLO-2 trial came about. SOLO-2 is a phase III randomized control trial evaluating olaparib versus placebo in patients with platinum-sensitive recurrent ovarian cancer after 2 lines of platinum-based chemotherapy. In this study, patients were germline BRCA1 or BRCA2 positive. They found a significant increase in progression-free survival with olaparib as compared to placebo, around 19 months versus 5.5 months.

Even though this trial evaluated patients with BRCA germline mutations, the data from this trial as combined with Study 19 allowed for the broad label of olaparib in a maintenance setting. It was approved for patients with platinum-sensitive recurrent disease as a maintenance drug regardless of BRCA status. The other important thing about the SOLO-2 trial was that it evaluated tablets as opposed to capsules. Previously, patients were taking up to 16 capsules a day for the BID olaparib dosing. With this trial, the results showed that the tablets were just as efficacious, and now patients are able to take 4 tablets daily as opposed to 16.

Matthew Powell, MD: Michael Friedlander presented the data for SOLO-2 looking at a rather eloquent analysis of time without symptoms or toxicity in that data cohort. I think it really gave us good evidence that these drugs are not providing undue toxicity, and even when we look at the quality-of-life—adjusted progression-free survival, there still seems to be a very nice statistical benefit of the use of olaparib in this maintenance indication. These patients had a progression-free survival advantage of 15 months versus 5 and a half months, and even when you adjust for the differences in quality of life, this still held up as statistically significant.

Oliver Dorigo, MD, PhD: Olaparib as a maintenance therapy has now been studied in a couple of very large trials that were conducted in patients with platinum-sensitive recurrent ovarian cancer. What we have seen in these trials is that maintenance olaparib therapy provides a very meaningful increase in progression-free survival for particularly those patients who have BRCA1 and BRCA2 mutations in their germline.

Though the initially studied cohort included ovarian cancer patients agnostic of BRCA and BRCA2 genetic mutations, we then in an exploratory analysis noticed that those particular patients with BRCA1 and BRCA2 mutations did respond much better to olaparib maintenance therapy compared to those patients that didn’t have germline mutation in those important genes. The follow-up studies with olaparib then focused largely on those patients who had BRCA1 and BRCA2 mutations and showed that the progression-free survival was a mean of 19 months versus about 5 to 6 months in the placebo-treated group.

Transcript Edited for Clarity