Ovarian Cancer: Significant Clinical Trials

EP: 1.Molecular Testing and Ovarian Cancer

EP: 2.Sequencing of Biomarker Testing for Ovarian Cancer

EP: 3.Genetic Counseling for Ovarian Cancer

EP: 4.Case Scenario: Stage 3A High-Grade Epithelial Ovarian Cancer

EP: 5.Starting Maintenance Therapy for Ovarian Cancer

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EP: 6.Ovarian Cancer: Significant Clinical Trials

EP: 7.Case Scenario: Stage 3C High-Grade Serous Ovarian Cancer

EP: 8.Ovarian Cancer Maintenance Therapy: Olaparib vs. Niraparib

EP: 9.Ovarian Cancer Maintenance Therapy Clinical Pearls

EP: 10.The Future of Ovarian Cancer Treatment

Chad A. Hamilton, MD: You mentioned several of these pivotal trials that we’ve seen in the past few years that led to the registration FDA [Food and Drug Administration] indications for these maintenance therapies. You had mentioned earlier that we all do these cross-trial comparisons. I’m thinking specifically of PRIMA, SOLO-1, and PAOLA-1 that got us the frontline indications. The thing I do remind myself about is, as you mentioned, that the PRIMA population did seem to be a higher risk, higher volume disease initially, and that was an all-comers population. Where SOLO-1, not to be hyperbolic about it, kind of blew us all away having shown a 70% reduction in progression of disease. That’s something we haven’t seen, and I haven’t seen in my career. Then, to have PRIMA follow-up with an all-comers population, granted a little bit heavier disease burden and a little bit higher risk population, PRIMA also had fairly dramatic decreases in progression and death in those patients. Forgive me if these numbers are off, but I think it’s in the high 50s-60s range based on HRD [homologous recombination deficiency] or BRCA status. Those are pretty remarkable results, and even in the PRIMA exploratory analyses in the patients that were HRD positive, maybe not without BRCA, and also the proficient population, we saw activity of the PARP [poly adenosine diphosphate-ribose polymerase] inhibitors there. Those are things that have really stuck out in my mind and in my practice, things that I talked to our colleagues about. Regarding PAOLA-1, I agree with you. When I’ve started a patient on bevacizumab [Avastin], then I usually will stick with it, and I’m a pretty strict constructionist when it comes to guidelines and FDA approval. If I’m going to layer on a part, I layer on olaparib [Lynparza] with that, and I do think there’s a benefit there. I think a lot of it is probably driven by the by the PARP inhibitor in that circumstance just like you alluded to. I’m sort of a big picture guy. Those are the big picture sort of things that I think of when I think about these various trials that got us the first-line indications and has really had a dramatic impact on our patients. Is there anything I’ve missed or anything I’ve skipped at a sort of broad level that you think about when you think about PRIMA, PAOLA-1, or SOLO-1?

Robert W. Holloway, MD: I don’t think so. I think I practice very much the same way. I think the difficult group we haven’t mentioned in the examples here is the wild type, HR [homologous recombination]-proficient patient. What do you do for them? I wish we had something better. There is a benefit with PARP in the PRIMA trial with niraparib [Zejula], as you mentioned, and there is a benefit with bevacizumab. Unfortunately, that didn’t work out in PAOLA-1 for that combination. It didn’t provide a benefit over bevacizumab alone, so the benefit is relatively short compared to what we see in the HRD population. It’s a tricky calculus, which I think you have to kind of look at the side effects, complications, and quality of life, and then individualize if you’re a patient and have that discussion about “here are your options.” Recognize that whichever path you take, you’re probably going to use the opposite one when they relapse. Hopefully you get a platinum-sensitive relapse, and you’re going to have the opportunity to use the other one. So that’s the tricky calculus, I think in the proficient patient group.

Chad A. Hamilton, MD: As we started wading into this field of maintenance and got more and more indications, I started asking myself and others, “Should everybody get maintenance therapy of some sort at this point? Are we at that point in our practice?” I think maintenance is right for a lot of people. In that proficient population I have a little bit more of a conversation with the patient about the potential pros and cons of maintenance therapy for them. I have some patients that are proficient that I have treated with part maintenance, and I have others that I have not. I guess that’s the population that I really tried to individualize, and that may be the toughest group to educate on the pros and cons of PARP. I do worry about the cost of maintenance for everybody, especially this proficient combination, until we have some better indicator of who is going to benefit. A little bit of that goes with the bevacizumab/olaparib combination as well, if we get most of the bang for the buck from PARP. It hasn’t changed my practice, but it’s in the back of my mind when I think about these things.

Transcript edited for clarity.