Ovarian Cancer - Episode 7

Case 1: Impact of Biomarkers on Maintenance Therapy

Targeted Oncology

Chad Hamilton, MD: ESMO [the European Society for Medical Oncology Congress] was a game changer with all of this. I go in a different direction than you, Tom. This patient fits neatly into that. This is the PRIMA type patient, so I would have gone carboplatin/Taxol [paclitaxel] first. Then another question is how soon you start your maintenance after primary chemotherapy. Then I would have transitioned into single-agent niraparib. We’ve been doing that since ESMO, certainly with the publication, but it’s all the more easy to do it now with the FDA indication, and it’s nice to have the nod from the FDA with the modified dosing as well with the 77-kg weight and 150,000 platelets to triage your patients. We were moving in that direction before, but the data keep bearing out that that’s a reasonable thing to do for these patients.

You made the statement that you wouldn’t observe anyone anymore, Tom. I’ll pose it to Shannon: are we in a day and age where observation is a thing of the past, or is there still a role? Where are we right now?

Shannon Westin, MD: It depends on the patient. I know we can certainly argue this point, but everybody needs to hear about maintenance options, and whether they choose to pursue them, that’s up to them. I feel strongly that patients with BRCA mutation or HRD [homologous recombination deficiency] definitely need to strongly consider utilizing maintenance if they’re up to it. For the HRP [homologous recombination proficient] patients, I still talk to them about it. If they were started on bevacizumab, I continue it, but if not, I discuss the details around the PRIMA data as best I can. There’s a population that is HRP, at least based on testing, and this gets at what you were talking about, Tom, where the testing isn’t perfect. There are patients who benefit from PARP inhibition who are not identified by our testing strategies. Why is that? Is that because they have some other marker we don’t know about? Maybe. Is it because our testing strategies don’t identify every single patient who could benefit? Yes, obviously. I’m interested in doing a deeper dive on those so-called HR-proficient tumors that did get a benefit from niraparib.

What I tell patients is this: “There may be a chance you could benefit from this drug. Your testing says not that much; it might be a little bit, but you may be in that population that we don’t know yet, that could get a benefit,” and I let them decide. Some patients say, “I’d rather take something, and even if it only gives me a few extra months, at least I did what I could,” and that’s reasonable. I talk to everybody about it, but for those HR-proficient patients, I’m not as pushy as I am with the patients who have a biomarker.

Thomas C. Krivak, MD: I completely agree. Biomarkers are the way to go. You present it and let them make a choice. What is interesting and what I love about PRIMA, and subset analyses are always fun to look at and immature data are always fun to look and talk about, I love how the hazard ratio is flipped. The HRP group in the overall survival had the best hazard ratio, and it had the worst hazard ratio in the PFS [progression-free survival]. As we see those data mature, but there’s no doubt about it: the HRP group, and if people believe in HRD and testing, some people don’t. If you don’t believe in HRD testing, I don’t ever want to hear anybody comment about what an HRP patient is because if you don’t do the test, you’re not going to know who HRP is. In the same term, “I don’t believe in HRD testing.” “What’s the highest unmet need?” “The HRP proficient group.” Well, hold on a second. If you’re going to say that, you have to do the test. You can’t say both.

Chad Hamilton, MD: I agree with you, Tom, but it is important to continually highlight that a cell is either HRP or HRD: it’s a yes or no, and it may not be a fixed state. But the testing is only an indirect indicator of that. It does not give us a yes or no. That’s more of a challenging thing to wrap our head around. We have to continually remind ourselves that, while the cell is either HRD or HRP, the testing is all cutoff; some of them fairly arbitrary and different for different tumor types. They all have to be interpreted with a lot of caution, and we’re seeing that these studies are demonstrating that we don’t have a perfect fix on what that is.

Transcript edited for clarity.