Oral Oncolytics Landscape Across Cancer Types

Bruce A. Feinberg, DO: Hello, and thank you for joining this American Journal of Managed Care Peer Exchange video program on oral oncolytics. During this panel, my colleagues and I will discuss the costs of oral oncolytics and explore the variables that affect their use in healthcare.

My name is Dr Bruce Feinberg, and I am vice president of clinical affairs and chief medical officer at Cardinal Health Specialty Solutions. Joining this distinguished panel is Dr John Fox, senior medical director and associate vice president of medical affairs for Priority Health in Grand Rapids, Michigan, and Dr Bruce Gould, medical director of Northwest Georgia Oncology Centers in Marietta, Georgia, and president of the Community Oncology Alliance. Thank you, again, for joining us. Let’s begin.

Is the oral oncolytics story really a prime time story? There’s a lot of data that say yes. They are now 25%, 35% of all new oncology drugs in development. Numerous studies suggest (and this is mostly survey-type studies) that patients prefer orals to infused—perceiving them as less toxic. Regimens, though, can cost $5000 to $15,000, not really differentiating them from infusion-based treatment. More importantly, [the] average out-of-pocket cost for orals [varies] widely, often more than the infused agents, ranging from 25% to 50% of total cost. There’s a question of adherence and compliance with orals that doesn’t seem to impact the infusion world.

So, as we get into the topic, let’s start with that first question. It’s [been suggested] that orals are going to take over the treatment of oncology, and that’s been going on for the past decade. But, if we look at all of the breakthrough drugs that have come out—5 in chronic myeloid leukemia, 5 in renal cell—are they really making an impact? Breast, colon, lung, lymphoma—we’re not seeing the big cancers being impacted by this field. So, are they ready for prime time? Bruce, from the practitioner’s perspective, are orals a big deal?

Bruce J. Gould, MD: I would say they are. As you said, they are 25% to 30% of the new drugs in the pipeline. Clearly, in 2016, we probably have 40 to 60 oral oncolytics that we didn’t have 20 years ago. As you pointed out though, a lot of these new oral oncolytics are kind of clustered in less common diseases like CML (chronic myeloid leukemia) or renal cell cancer. There’s relatively fewer oncolytics in the big diseases, such as colon cancer, lung cancer, and breast cancer. But, at this point, clearly there’s going to be use of both types of drugs—parenteral and oral oncolytics. I think that will continue into the future.

Bruce A. Feinberg, DO: John, from the payer perspective, now with orals we get to a pharmacy benefit instead of a medical benefit. Are payers really focused on that pharmacy benefit in oncology? Is it distinguished enough that it stands out or is it the big picture? Which kinds of oral drugs, especially biologics, have really been an issue? How do you look at it?

John L. Fox, MD, MHA: For our health plan, we’re at risk for all drugs, whether or not they’re under the medical or pharmacy benefit. If you’re a specialty pharmacy or you’re a PBM (pharmacy benefit manager), you may just have risk for the pharmacy—their oral benefit. So, from where we’re sitting, I’m relatively indifferent to whether or not it’s oral or intravenous. The cost is the cost.

Bruce A. Feinberg, DO: That makes it easy.

John L. Fox, MD, MHA: Yes, it does. I think the dilemma, though, is the extraordinary cost in our plan. Fifty-five percent of the total trend is due to drugs. It’s both medical benefit drugs and pharmacy benefit drugs. So, at the end of the day, it doesn’t really matter. Cost is cost.

Bruce A. Feinberg, DO: What makes a drug applicable to an oral delivery is generally that it’s a small molecule. Small molecules are generally molecules that are going to be able to cross a membrane, and that has put them into the molecular pathway process where they’re interacting with a pathway inside of a cell. That puts us into the world, now, of precision medicine.

To some extent, you would think that the wave is there. Precision medicine is the future, and small molecules are only going to increase in number. But, the more precise we get, typically, the more refined a population. So, we see small molecules coming into lung cancer, but echinoderm microtubule-anaplastic lymphoma kinase (EML-ALK) fusion protein patients represent maybe 2% of adult lung cancer patients. EGFR (epidermal growth factor receptor) mutation patients represent maybe 3% to 5%. So we see a lot of interest and a lot of hype, but the impact seems to be small. Now it’s being challenged with immuno-oncology.

So, for the world of the splitters, we’re splitting out every single possible molecular pathway and finding a drug interruption. We get into the world of lumpers. It’s all immune system—regulated. Where do you think it’s going, and how will that impact what the orals look like in the future?

Bruce J. Gould, MD: Well, years ago when I was a fellow, I asked a well-known researcher from Fox Chase, “Are we ever going to have a cure for cancer?” His answer was, “We’re going to have many cures for cancer.” I think that’s the point to which you’re speaking.

Cancer is a very complex disease, and there’s going to be many different ways of treating it, whether it’s [through] orals or parenteral, whether [with] immunomodulators that are applicable to many various diseases or with very targeted therapies that only work in a very select population. Again, I think this is what is making oncology so darn complex. There’s going to be very specific ways for treating very specific cancers, and it’s going to depend on whether there’s specific mutations that you can target. If not, then we’ll probably attack those with broader therapies.

John L. Fox, MD, MHA: Even more to that point, as cancer becomes a chronic disease, we now have the opportunity for second-, third-, and fourth-line therapies.

Bruce J. Gould, MD: Absolutely.

John L. Fox, MD, MHA: I recall a conversation with one of my oncologist colleagues about renal cell. He said renal cell used to be a fatal illness, and now it’s a chronic illness. I wait until they [the patients] progress on 1 drug and then I put them on another drug. I think that’s going to happen in many disease states, and multiple myeloma is an example where we’ve got 8 or 9 different drugs now that we can use in different combinations and different sequences. We don’t know the right sequence, but I think that’s the other thing that’s adding to the cost. We’re improving survival, but that improved survival results in additional cost.

Bruce J. Gould, MD: Speaking to your point, one could imagine a situation like lung cancer. If you have a patient that’s ALK- or EGFR-mutated, you would use a targeted therapy for that patient. Then, when they progress, you go to chemotherapy. Then, after chemotherapy, you go to an immunomodulator. So, you’re using both therapies for a single patient.

Bruce A. Feinberg, DO: For those pharmaceutical companies who are listening right now, and who are manufacturing immuno-oncolytics, they would like you to go from a precision therapy to an immunotherapy and then to chemotherapy—just to make sure that you recognize that [there are] different ways to go?

Bruce J. Gould, MD: Yes.

John L. Fox, MD, MHA: And, unfortunately, now that we have all of these different options, we don’t know what the right sequencing is.

Bruce J. Gould, MD: Right.

John L. Fox, MD, MHA: We have a lot of different options. We have studies that say, “We’re going to use therapy X first, and then therapy Y following that.” But, there are too many permutations to know what the right sequence is today. You could never do those studies.

Bruce J. Gould, MD: That’s a good problem, but a very new problem for oncology. That’s one of the reasons that we don’t know [an answer], and we have had an explosion of new drugs over the past 10 years. Now, it’s a matter of letting the clinical studies catch up so we know how to sequence them properly.

Bruce A. Feinberg, DO: So, you’re getting into this big question of the positives and negatives that become involved with this explosion of oral therapeutics. Part of that, I guess, addresses a couple things. One is the chronic nature: the suggestion that orals are also potentially less toxic, as well as provide more options, because as we get into these more refined pathways, you get a refined pathway interruption and alternative refined pathway interruption. Then, you get into something which is more of a generalized treatment, like immunotherapy or chemotherapy. Do you perceive them, now that you’re using them, as less toxic? Are they just an alternative, or are they a different animal?

Bruce J. Gould, MD: I think that, for the most part, oral oncolytics can be just as toxic, if not more toxic, than parenteral therapies. For a drug like Gleevec (a relatively well-tolerated therapy), when you start looking at the tyrosine-kinase inhibitors, those, in my experience, have been very toxic drugs with bad skin problems, bad nausea, vomiting, diarrhea, and all sorts of problems with hypertension, and so forth.

I think it’s very important that when we talk to our patients about oral therapy that we educate them that they are not like taking an antibiotic or vitamin pill. They are very serious, potent drugs that need to be monitored carefully. The patient needs to be aware of the side effects and report them immediately should they occur.