DR LOVE: Can you talk a little bit about some of the data that was presented at ASCO in ovarian cancer, particularly related to the issue of neoadjuvant therapy and intraperitoneal therapy, that you think are important for docs in practice to know about?

DR HERZOG: There were a couple of really interesting trials. One that was done was looking at the whole concept of prolonging the platinum-free interval with using an active agent beyond platinum itself. This was a MITO-8 Phase III trial. It was an oral presentation at ASCO that was fairly interesting because there’s been a concept out there that’s been advanced that, for those patients that are intermediately platinum sensitive — in other words, they recur between 6 and 12 months — there may be benefit to using a nonplatinum agent so as to extend the platinum-free interval such that when they’re reintroduced to platinum, you’ll actually see a higher response rate, thereby providing them with a longer survival. And so that’s the thought behind this, is that you’re going to actually have a hypothetical advantage by doing this.

The question, though, that remains is, is that really the case or not? And so what MITO tried to do — and I say “try,” and we’ll get to why I say “try” in a minute — was to try to really compare actual survivals then for those patients in which they were randomized to receive a nonplatinum versus a platinum for those that recurred in that 6- to 12-month window, and followed these patients for the second recurrence, and then calculated their PFS2. And they also looked at overall survival for these patients.

And what they found was that the patients actually seemed to trend better for those who received a platinum in that 6- to 12-month group, going against what many people had advanced as a hypothetical advantage of receiving a nonplatinum in the 6- to 12-month group.

The conclusions were very strong. The concern that many people have is that, how valid are these conclusions? And there’s a couple of things that you need to understand about the study. One, it was closed prematurely, which is really important. The other thing is the primary endpoint was approaching statistical significance, but it indeed was 0.06. And certainly there’s cause for concern that administering a nonplatinum in that 6- to 12-month group may not help and, in fact, could even hurt.

But I don't know if we have enough strong data to say that that’s absolutely true. We don’t know what selection bias went into this. We don’t know, for a study that’s been done over the course of years, how that has changed with the current therapies and current approaches to treatment. So I think there’s a number of unanswered issues.

There were some interesting things raised in the discussion. And I think Maurie Markman was the discussant. And one of the things that was really interesting to me was there was a big pushback to “Why hasn’t this been done before? We’ve been presuming that this could be of benefit. We should have tested it. This is something we should have tested.”

Interestingly, we had a proposal on the table to test this for GOG probably 15 years ago or more. And it got closed when ICON4 came out. It was a study that was open for just a couple of weeks. We tried to test this. And it was still a very legitimate study, and that’s what we told people at that time. And they said, “No, we’re married to using a platinum-based doublet in that group no matter what.”

Clinicians went a different direction with that 6- to 12-month group without ever really testing that, and that’s where we ended up. And so I think it should be pointed out that we did try to test that. And the powers that be at the time did not want to do that. So I think that’s an important caveat of this particular study. I think we need to look, take this data and put it into context to the fact that it was a trial that didn’t completely enroll and didn’t hit its primary endpoint. But it is informative. It is something that I think is important for us to think about.

Treatment strategies in the management of ovarian cancer (OC)

Mechanism of action of PARP inhibitors and importance of BRCA testing

PARP inhibitors as primary treatment after multiple lines of therapy

PARP inhibitors as maintenance therapy

Tolerability of olaparib

Treatment options after olaparib failure

Differences among PARP inhibitors

Future directions in OC research