Kathleen Moore, MD: When you are considering…or starting a patient on a PARP [poly ADP ribose polymerase] inhibitor, really careful patient counseling and setting accurate expectations for your patient is key. It’s 100% of the battle because most of the time our patients have never seen an oral agent. And most of the time they’re really excited to try an oral agent because they’re tired of infusions. So they’re expecting an oral agent to sort of be like taking a Tylenol, and so if we give them a prescription and let them go off with that expectation, they’re going to all discontinue PARP inhibitors because it’s certainly not like taking a Tylenol. So you really have to set expectations well.
I talk about first, depending on which PARP I’m going to use, how it’s dosed. If it’s dosed twice daily with olaparib and rucaparib, if it’s dosed once daily with niraparib, I talk about the time of day. With niraparib, I talk about taking it at night, and I usually pre-medicate early on with an anti-nausea medicine, so they can just sort of sleep through any nausea and that helps ameliorate that toxicity. So I talk about timing.
I talk about what to expect. Nausea is low-grade, but feeling queasy every day isn’t great, so how do you overcome that? Fatigue. The fatigue is real, and it feels different to patients. They’re not used to feeling that low-grade energy every day. It’s very different than infusional chemotherapy. So they may think they understand fatigue, but then it feels different to them and they get anxious about that.
So talk about fatigue and then ways to overcome fatigue, such as staying active. I’m from Oklahoma, so there are herbal teas and things that patients like to try. It’s not counteractive with the PARP inhibitors, so I’m fine with that. It gives them something to try and often it makes them feel better and empowered that they’re doing something. So just make sure you know what your patients are taking. Really go through the low-grade, most common toxicities, which are nausea and fatigue. I do talk about dyspepsia and then diarrhea versus constipation and how you can overcome those. I send patients home with a prescription for an anti-nausea medication. Not everybody does, and that’s fine.
You can choose to let patients see how they feel, and then make a quick call and they get a rapid response. I tend to start it for 1 to 2 months, and then once we’re fine and rolling and people feel comfortable with the dose that they’re on, I try and wean that off. Because no one wants to be on Zofran [ondansetron] for 2 years. So I tend to start it, so that you don’t get into that cycle of nausea, and then pull it off. But that’s not something you must do. It’s just an idea.
We’ve done a lot of training with our office staff, so that they feel comfortable assessing toxicities for patients on PARP inhibitors. We have clinical pharmacists who also take those calls, so we’re very fortunate they can help with dose modifications, even if I’m not there. Today I’m not there, but if one of my patients calls she’s going to get completely appropriate feedback on what her symptoms are. And if someone feels like she needs to hold, they’re going to tell her to hold. So really education of the office staff is key because initially these patients will call with a lot of questions and concerns about the adverse events, and you have to be able to provide reassurances and action plans for things that need an action plan, or they’re going to come off because they don’t feel great on it. So I think setting expectation and having a plan for those key adverse effects is really key.
I do think that as a part of counseling for PARP inhibitors we have to talk about the risk of AML [acute myeloid leukemia] and MDS [myelodysplastic syndrome] because it’s sort of all over the concerns of PARPs. And it is real, but it’s low. It’s 1% to 2% across all programs. If you’re in that 1% to 2%, that really stinks though and it’s not a fixable problem. It tends to be often a terminal event for our patients. It’s likely that there are risk factors that set that patient up for developing AML or MDS that we haven’t been able to identify yet, although we’ve tried.
AML, MDS with PARP inhibitors is an early event. We see it like between 1 and 2 years. Usually it’s not an event from 7 years of PARP inhibitors. So there is something that patients are at risk for that we tip them with the PARP. But it is a low risk and so patients need to know that, they’re owed that. We talk about the 1% risk of bowel perforation with bevacizumab, so we better talk about the 2% risk of AML, MDS. So I don’t harp on that, but I do make sure patients have heard it. But mainly I talk about the low-grade adverse events and mitigation strategies.
Adherence to PARP inhibitors is key. If you’re not taking them, they don’t work. And we know from the breast cancer literature with hormonal agents that patients don’t always take their medications. They stop when they’re on vacation, they do all sorts of things that we don’t know about, although now we’re studying it, so we’re figuring it out. So I think if patients aren’t taking the medicines, they’re not helping. It all comes back to setting expectations appropriately with patients and being very responsive when they have concerns and reassuring them about the low-grade adverse events. For example, several of the PARP inhibitors have low-grade dyspnea as an adverse event. It’s very low grade, but it’s real. Patients feel a little dyspneic.
If they know it’s an adverse event of the drug and not that, “Oh, my pleural effusion is back or my cancer is coming back,” they’re usually fine with that. They think, “Oh, I can live with this as long as I know it’s not my cancer.” On niraparib, you can get some low-grade tachycardia. Patients feel it and we can treat it, but if they are worried that something bad is happening to their heart or they’re having a pulmonary embolus or the other terrible things that happen to our patients, they’re likely to get anxious enough to come off. So it comes down to setting expectations with patients and really responding, when they call, to their complaints and providing quite a bit of work-up. If you’re not sure if it’s medicine related or disease related, sometimes their disease is coming back and we have to respond to that. And provide reassurance when you realize it’s not, so they can stay on.
If you look at the studies, it’s again very consistent across the 3 studies that patients do not discontinue maintenance PARP inhibitors due to adverse events very frequently. It’s around 11% to 13%, which is pretty low compared to bevacizumab maintenance. That discontinuation rate is over 20%. And we think bevacizumab is a very well tolerated drug, and it is. It’s a great drug, but patients discontinue it because of the bone pain and the other sorts of things 20% of the time. So this is only half. So at least the study population is on and they maintain for as long as they need to. We’ll probably see a little higher rate as it rolls out into general population, but it’s not a drug that patients are telling us about. Sometimes they vote with their feet when they don’t like something. We’re not seeing that with PARP inhibitors, so I think that providers are likely doing a very good job doing what I’ve talked about because we don’t see high rates of discontinuation.
Transcript Edited for Clarity.