Case 1: Factors for Selecting First-Line Maintenance Therapy in Advanced Ovarian Cancer
A panel of experts share insight on patient factors to consider when selecting first-line maintenance therapy for advanced ovarian cancer.
Thomas C. Krivak, MD: Coming down to the third question here, safety, efficacy data used to help guidelines, help develop your treatment, how you distinguish niraparib [Zejula] from olaparib [Lynparza] from olaparib plus bevacizumab [Avastin], similarities, differences in design trials. How do we look at all this information? For the longest time, all we had was like bevacizumab, or carbo/taxol [carboplatin, paclitaxel], and then in the last 5 or 6 years we’ve had numerous medications, similar activity with excellent progression-free survivals, excellent hazard ratios. How do we now tease out? Do we take the science of all these studies and then take the art of our medicine and taking each of these scientific articles and trying to apply it to that each individual patient? John, how are you doing that with the niraparib, olaparib, olaparib/bev [bevacizumab]?
John K. Chan, MD: This is an unprecedented time where we’ve never had so many number of drugs, new mechanisms of action, combinations of using these drugs for our patients. We almost must come up with particular algorithms for our patients and, like Cecelia was saying, the ability to personalize medicine given all these options for our patients is just wonderful for our patients. Given this similarity and design of these populations, without a full cross-trial comparison to look at all these agents, all of them upfront, I use the information that we have, and for distinguishing the drugs, I tend to use olaparib in the upfront setting in germline positive or somatic positive patients based on the magnitude of benefit that we saw with the SOLO-1 results. I get it. The patients who were in the PRIMA trial are a different group. They are a more heavily pretreated group. They are a group where they had more neoadjuvant [therapy]. It’s difficult to compare apples to apples when the patient populations are different between the 2. But I do think niraparib is a great option for our patients as a single agent when they have homologous recombination deficiency [HRD]. Nevertheless, the combination of olaparib and bevacizumab was able to achieve a 37-month progression-free survival benefit in that combination. With that, that doublet agent is also a good option for the patients, albeit with 2 agents, and using 2 drugs the toxicity is going to be higher, and their discontinuation rate is also a significant consideration. That’s how I differentiate the use of single agent olaparib, niraparib, and also the combination of the olaparib and bevacizumab.
Cecelia H. Boardman, MD: Tom, take into consideration some patient factors. If you look at a patient and you look at the trend in their labs over the course of their chemotherapy, and if they struggled with platelets and their platelets returning to baseline, maybe niraparib isn’t your first choice, or maybe you start at 200 mg on niraparib instead of 300 mg. This patient particularly, she meets that weights and plates criterion. She’s under 80 kilos. If we were going to go the niraparib route for whatever reason, you would start at 200 mg a day, not 300 mg. If a patient struggles with anemia during their chemotherapy, obviously Lynparza has a higher incidence of anemia associated with it. I might lean towards niraparib in that patient rather than olaparib if anemia has been a big consideration, like my Jehovah’s witness who will not accept a transfusion, and if her hemoglobin goes down to 7.0, I’ve got some difficulty in terms of continuing that therapy.
Patients with significant hypertension, proteinuria, renal insufficiency, you’ve got to look carefully at the choice of bevacizumab in those patients, and either be proactive in managing their hypertension, renal function, and watching their proteinuria, or you may say, you know what, maybe you’re not a great candidate for bev[bevacizumab] based on your medical comorbidities. Looking at that piece of how they move through their primary therapy also helps you to tease out which treatment may be the best on an individual basis for adverse effects and medical comorbidities.
Thomas C. Krivak, MD: Absolutely, love what you guys are saying not just because I agree with it and I agree with everything you’re saying, but to me, it’s just exciting to be able to have these medications. The other thing, too, how you’re talking about if somebody has got a massive DVT [deep vein thrombosis]/PE [pulmonary embolism] we may not want to use bevacizumab, we’ll use niraparib, or if they have bad thrombocytopenia, use olaparib instead. The other thing I look for, too, is patients who go through treatment, if somebody would have significant adverse effects, we now can switch them. It’s important, and I don’t know if you guys use 2 years of therapy or 3 years of therapy, we’re still trying to battle the timing out, but there’s no doubt about it, these patients need to be on these medications for probably at least 2 years, and if somebody is suffering toxicity on bev [bevacizumab] we’d have to take them off and there’s nothing else to use. You’d have to go to carbo [carboplatin] or taxol [paclitaxel] or something. Now we have medications that we can interchange. I really love how you guys are looking at these patient factors and how you guys are thinking. It makes me feel good because that’s how I think as well. To me, it’s about selecting the right medication, starting them on it based off clinical and biologic factors, and then if they would have toxicity, managing that toxicity, and then if they can’t stay on that medication, potentially switching them to another medication within that class. This is fantastic for our patients.
We talked about the criteria for maintenance therapy, this last fourth question, but I also want to get, as a clinician, a lot of patients will talk to me about certain things and stuff, but it seems to me that the patients always want to say nice things to their doctors, and I’ll get asked to leave the room and then the patients want to talk with like the PAs [physician assistant]. I’m curious, Ashley, how do the patients, like when you see the patients say, “Dr Krivak, you can leave, I want to talk to Ashley.” Are these patients talking to you about adverse effects? Are they OK with the medications? Do you think they’re happy because their CT scans are negative, their CA 125s [cancer antigen 125] are normal and they’re just glad they’re cancer free? I get asked to leave the room quite often and they want to talk to you. I’m just curious as they go through, what kind of interactions or what do they say to you about maintenance therapy and how they’re doing it?
Ashley Farione, PA-C: Right. When you leave the room, we talk about adverse effects. They tell me they’re having nausea, vomiting, diarrhea, things like that, about their counts and how we have to treat that. Then sometimes we talk about symptom management, different medications they can try for nausea, vomiting, things that they could try for fatigue. I tell them about supportive measures. They can do exercise. We have those general conversations usually. But a lot of the times, I feel like, too, the patients, when they’re on a PARP, they feel like they’re glad to be on it because they know that they’re still being treated. I feel like a lot of the times when they’re approaching that 2- or 3-year mark is when they start to get a little anxious, like, well, I’m going to be going off the PARP, what next? What do we do next? Shouldn’t I continue it? And they want to continue something. I feel like towards the end of it is when they start to get nervous about it, and then that brings up questions like why can’t I keep staying on it? A lot of the times it’s just maintenance and symptom management, but I handle all that.
Thomas C. Krivak, MD: Good. I’m glad to hear that. I do agree, some patients are getting nervous. I have a patient who came off Tuesday, stopped niraparib. She stopped it on Tuesday and she’s nervous, but she’s NED [no evidence of disease] 3 years out afterwards. Think about it, when we were fellows, John and Cecelia, we were putting people on 182, and by 3 years most of the patients had recurred, you know? I mean it’s amazing, 3 years, and she was homologous recombination proficient [HRP]. She was an HRP patient. She has an HRP tumor that she’s done very well.
John K. Chan, MD: Tom, I have 1 more thing to add. One of the reasons why we’re pretty good at offering these patients maintenance upfront is because we put a lot of these patients on trial for recurrent maintenance, platinum-sensitive maintenance, and the indication for all these drugs came aboard for us in the recurrent setting already, where they were on treatment until disease progression. All of us probably have a handful of these patients where they’ve been on maintenance for their recurrence for 4 years and they’re afraid to stop and they’re doing OK in terms of toxicity, and we’re the ones that are concerned because long-term use of these drugs and the adverse effects in terms of their bone marrow. In terms of adopting to the maintenance strategy, it came aboard a lot for us because we were doing this already in the recurrent setting based on the FDA [Food and Drug Administration] label.
Thomas C. Krivak, MD: Yes, OCEANS and Study 19, NOVA.
John K. Chan, MD: Yes.
Thomas C. Krivak, MD: Yes. They’ve all been very, very positive.
John K. Chan, MD: Yes. One other question, since you were saying, a lot of times when we leave the room, it’s between the nurse and the patient. Ashley, I was wondering, how often do patients bring up discussions regarding financial toxicity of these drugs?
Ashley Farione, PA-C: Sometimes they do. They’re always worried about cost and everything like that, and sometimes they’ll even bring up costs about testing with the genetics. But I feel like for the most part, I mean I don’t do a lot of the [prior] authorizations for the medication or anything like that. Our nurses who we work with are fantastic and they usually take care of that. But usually, we get the medications and everything, for the most part approved. Dr Krivak, I don’t know if you agree with that or not, but I mean they’re worried about it upfront, but then our office usually works it out and then they help them with the finances. I don’t know if the patients are responsible for a lot of it or not afterwards because it gets approved and then I don’t hear much of it after that it gets approved. I don’t know. Dr Krivak, do you know anything about that?
Thomas C. Krivak, MD: The companies have been supportive. I agree, John, we always have to think about financial toxicity. I do think that for a certain degree, in Pennsylvania, it seems like the insurances, at least in Pittsburgh, Pennsylvania it seems like it’s a competitive market and there’s not a lot of declining. We’ll use medications off-label quite a bit and it’s either (a) covered by insurance or (b) compassionate or the company will give the medication for free. To me, it’s something that we always got to be considering. There’s no doubt about it. I would agree with Ashley, she probably gets asked that as well as the nurses, I would say maybe about 10% to 15% of the patients. I do get the testing question, and that’s why I’m always double checking to make sure patients aren’t getting large bills for $15,000 or $30,000. The testing companies will always work with the patients as well because of that financial toxicity, you’re right. That adds stress to a time where they should be focusing on managing adverse effects, getting better, and recovering. That’s a good question, John.
Transcript Edited for Clarity
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