Ovarian Cancer - Episode 8
Thomas C. Krivak, MD:The dosing modification is important. We’d all agree that 3 PARP [inhibitors] came on the market fairly quickly; we’re all trying to figure out how to use these, and it’s nice to have choices for our patients, and it’s nice for responses as well as nice for [adverse] effect management. There’s niraparib, the body weight dosing, less than 77 kg, as well as the platelet count less than 150,000, it was a very important SPORE [Specialized Programs of Research Excellence] trend analysis in the NOVA [trial] that that got applied to PRIMA to help get a tailored dose. Patients who were above 77 kg and had a platelet count about 150,000 could start on 300mg and then be dose reduced, versus patients who had one of those would be started on a lower dose at 200mg. It’s nice to see that because what you can then see is hopefully decreased [adverse] effects, and that’s what we’ll see again inPRIMA. It was about a third of the patients who were started in the PRIMA trial who were allowed to have the individualized dosing. Some of the patients still got 300mg. It’s not that we started an individualized dosing and everybody got 200 mg. No, if you met the criteria for 200mg, then you got 200mg, and if you met the criteria for 300 mg, then you were started at 300mg. And if you didn’t start at 300mg, that would have been a protocol violation. It’s important to know that we’re trying to individualize the dose, which makes sense.
Then looking at the [adverse] effects, 300 mg, 200 mg, 100 mg: you can see the color coding, and you do see that there’s a difference in thrombocytopenia, which was one of the [adverse] effects that many of us were concerned about. I know that it did catch me off guard as I was learning how to use niraparib and all the PARPs. I thought the thrombocytopenia at times was a lot like gemcitabine/carboplatin where you’d start it, and the platelets would trickle down a little bit. You wouldn’t pay a lot of attention, you’d follow it. But you could see platelets at times fall fairly quickly. It was nice to see some of the individualized dosing. You can see the effects on anemia, neutropenia, fatigue, as well as hypertension. The individualized dosing has helped decrease the incidence of some of these [adverse] effects.
It’s important when looking at NOVA and with PRIMA that they looked at the individualized dosing to see that there was no difference in PFS [progression-free survival] for these folks. For patients who were started and underwent dose reductions, I like how they looked at PFS after month 3 to look at those folks to make sure they were on their titrated dose, to see that there’s no statistically significant difference in progression-free survival. I thought that this was important coming out of PRIMA, and that looking at NOVA going from the standard 300mg dose to then applying it to PRIMA to see that we could go ahead and apply this individualized dosing. Are you guys doing this in your practice, or how are you guys dosing niraparib based off PRIMA and NOVA for your patients coming in for treatment right now?
Shannon Westin, MD: We’re using the platelets and the body weight, for sure.
Chad Hamilton, MD: Us, too. Absolutely.
Thomas C. Krivak, MD: Have you noticed a decrease in [adverse] effects?
Shannon Westin, MD: Yes, there’s a population it works for. There is still a population that needs another dose reduction, but we are seeing less of that, to your point, profound drop in platelets that we were seeing after a few days on treatment. It’s a lot easier to keep patients on therapy.
Thomas C. Krivak, MD: That’s the key. The key is finding the right dose for being on it long term because we have these long-term responders who do well.
Any thoughts about Case 1? Treated very aggressively with surgery, IV, IP [intravenous, intraperitoneal] chemotherapy, and then all of us would have given her some type of maintenance.
Shannon Westin, MD: Yes.
Thomas C. Krivak, MD: I probably would have had her on bevacizumab because that’s what I prefer and would have added olaparib on. If she would have had any problems, then I would have switched over to niraparib.
Chad Hamilton, MD: What a fantastic opportunity to even be having this conversation. Think about 5 years ago where we were. We felt like we were just spinning our wheels for so long in ovarian cancer, and we have all these options now, that are good options. I’ve never heard the word unprecedented come up in so many talks, but that’s where we are at this point. The future continues with the trials that are on the horizon to further define better ways to treat these patients.
Transcript edited for clarity.