Oral Oncolytics: Exploring Challenges in Cost, Adherence, and Management - Episode 5

Next-Generation Sequencing in Oncology

Bruce A. Feinberg, DO: One of the things about orals is [that] because of this nature that most of them are precision or targeted drugs, they are tied to a molecular diagnostic. That companion diagnostic, or that mutation that’s been identified, has created this greater understanding that mutations are major drivers of cancer, and that they (targeted drugs) may not be restricted on an anatomic basis. So, it may not be a mutation that’s only found in breast [cancer], but it may be found elsewhere.

That’s led, now, to this consideration of next-generation sequencing as a means to test cancers for the mutations which may be considered atypical but nonetheless, if found, could then lead to a targeted intervention. It’s all hypothetical, right? But it’s being done.

From a payer standpoint, what’s your perspective on this? What’s the payer industry doing to address this? It could open up Pandora’s box of fourth lines, fifth lines, and sixth lines of treatment that have both the companion diagnostic and a drug cost. All of it is unproven but it’s so tantalizing because of the science.

John L. Fox, MD, MHA: First, to be clear, if there is a targeted therapy based on a molecular mutation, whether it be MET-ALK, or KRAS, or NRAS, or BRAF, or V600E, we’re going to pay for that. The cost of the test is miniscule in comparison.

Bruce A. Feinberg, DO: Where it’s proven to be clinically valid and clinically useful.

John L. Fox, MD, MHA: Right. The question of next-generation sequencing to identify potential agents [that might be effective] in a particular patient’s cancer is appealing because there are many cancers for which we don’t have adequate therapies—pancreatic cancer and ovarian cancer, for example. There are also patients who have good performance status who have failed traditional therapies.

The question is, do you guess at what could be used next and pick from the laundry list of National Comprehensive Cancer Network (NCCN) guidelines, or do you identify whether or not somebody has a mutation that makes them eligible for a clinical trial? As you know, the American Society of Clinical Oncology (ASCO) has their TAPUR trial. They have 8 or 12 different drugs that are [included] in [the] trial.

Bruce A. Feinberg, DO: Right, but it’s a restricted number of sites.

John L. Fox, MD, MHA: It’s a restricted number of sites, but unfortunately, you have to have a known mutation to be eligible for that trial. As a health plan, we decided to pay for that. We pay for participation in clinical trials, and it seems disingenuous not to pay for the test to determine whether or not you’re eligible for clinical trials. So, I think we’re not ready for prime time yet. Interestingly, the NCCN, in their non—small cell lung cancer pathways, recommends next-generation sequencing because there are different known mutations today.

Bruce A. Feinberg, DO: So TAPUR is a concept whereby ASCO is sponsoring a trial in which it doesn’t really prescribe what type of testing is done—[it could be] any kind of molecular testing. It could be full next-generation genome sequencing, but it could also be a very specific test. It’s going to be done. Then, they’ve gotten drug companies to pony up a free drug, so that the free drug can be given to a patient who has a matched target regardless of diagnosis. Exciting, but as we see often, what happens is the notion of a trial gets translated as it must be proven. “They wouldn’t be testing it if we really didn’t know that it worked.”

Bruce J. Gould, MD: Right.

Bruce A. Feinberg, DO: We see it happening in the community. Do you see that amongst your own doctors where they’re starting to describe that patient as “that younger patient [with] a great performance status—they failed standard of care?” “Let’s take a look and see if we can find the target. We’ll treat the target.”

Bruce J. Gould, MD: Yes, I see that all the time, and I’m not sure how this is going to be paid for [or who will pay for it]. For example, take a young lady who’s failed her 8 lines of chemotherapy for metastatic breast cancer. The breast cancer sample is sent off for next-generation sequencing and guess what, the patient has an abnormal androgen receptor that could be targeted.

A lot of these patients are being treated with Xtandi, a drug that’s FDA approved for the treatment of prostate cancer and is known to interfere with the activity of androgen receptors. [Although] it’s known in prostate cancer, it’s not really clearly known or understood [as to] how it works in breast cancer. But a lot of doctors, again, want to do the right thing for their patient and try to help them in any way they can. So, they prescribe these very costly drugs without really any clear understanding [whether] that drug is going to benefit the patient. Of course, that puts guys like Dr. Fox in a very difficult position [regarding] whether or not they’re going to pay for those drugs.

John L. Fox, MD, MHA: Well, I don’t think it puts us in a difficult position at all if there’s no evidence to support it. We say that if it’s FDA approved for that indication, or if it’s in an approved compendium like the NCCN, or if you can produce 2 peer-reviewed articles supporting the intended use, then we’re obligated to pay for it. So there is a level of proof that’s still required to cover in that circumstance.

Bruce J. Gould, MD: But, on the other hand, I’m sure you get heat from plenty of families on issues like this that I think would put you guys in a tough position.

John L. Fox, MD, MHA: Yeah.

Bruce J. Gould, MD: It kind of reminds me of the days back in the 1990s when the patients strong-armed--

John L. Fox, MD, MHA: Bone-marrow transplants for breast cancer.

Bruce J. Gould, MD: Yeah, exactly. It’s a similar type of thing.

Bruce A. Feinberg, DO: They were camping out and doing sit-ins on the Genentech campus. It got pretty serious. In all fairness to the era, when things weren’t working and there was this possibility that transplants were effective, you could see where it got out of control.

I understand the position you’re taking. I think it’s great because it’s codified. “Here are the rules.” We’re all playing by the same rule book, but I can imagine a member giving the call and, if the member isn’t going to be covered, then it’s an out-of-pocket cost and you’re going to leverage all your personal wealth for a treatment. That puts the pressure back on the doctor. Do you really want to tell that patient to leverage all of their personal wealth for that purpose?