Hope S. Rugo, MD, FASCO: One of the issues for us is always how payers deal with this. We talked about share of cost and how you decide what payers think about IV [intravenous] versus oral therapy in terms of invasive delivery as well as the concerns about the different treatments. Paclitaxel is now generic, but it’s IV. This drug will be new and oral, and not generic. John, can you tell us a little bit about what your perspective is on this?

John Fox, MD, MHA: Just to clarify, is it 2 drugs? You did describe the pill taking, but is it 2 drugs?

Hope S. Rugo, MD, FASCO: It’s 2 drugs combined. The product Oraxol includes oral paclitaxel, which is poorly absorbed because of the P-glycoprotein.

John Fox, MD, MHA: That’s in 1 pill.

Hope S. Rugo, MD, FASCO: No, actually. It’s a bunch of pills. There’s a little blister pack with 1 pill with the encequidar and then another blister pack with several gel tablets that have oral paclitaxel in them.

John Fox, MD, MHA: OK. So for the patient, another consideration, as you alluded to, is going to be the patient cost. IV paclitaxel, as you note, is generic, and even if patients don’t have cost coverage with a Medigap policy, they’re going to be paying a small amount of money. But for an oral therapy, if they have a Medicare Advantage plan or traditional Medicare, they’re going to be paying 25% coinsurance up until they hit their catastrophic coverage. Then they’ve got 5% after that. The cost of this, depending on what it is, may be prohibitive for some patients.

Even if patients have Medicare Part D coverage, they’re still going to have significant costs. For us as a plan, what we observe all the time is simply that if there is only an oral therapy, everybody thinks that the new IV is the cat’s meow because we can ensure adherence, and if there is only an IV therapy, everybody thinks that the new oral therapy is the cat’s meow because it will improve patient convenience. I think there is a mixture of both. I agree with Claudine that it’s nice to have an option. I think that fundamentally, though, Medicare is going to require that we cover this drug if it’s FDA approved.

Then we’ll have to allow that oral therapy. One exception is I don’t know how many of your practices or how many of your institutions are involved in OCM, the Oncology Care Model, through CMMI [Centers for Medicare & Medicaid Innovation]. Most of these patients who are on IV therapy can be coached through the toxicities, and if you’re in an OCM practice and now these dollars are coming out of your pocket instead of the federal government’s, it may be in the institution’s interest to try to coach those patients through the IV therapy.

There are a lot of private practices that are in OCM, and I’m confident that if they’ve got a generic paclitaxel IV compared with a drug that might cost $10,000 a month, they’re going to work very hard to try to get that patient to tolerate the IV paclitaxel.

Hope S. Rugo, MD, FASCO: Do you see a situation where the payers might—outside Medicare—say, “We would approve IV paclitaxel, but unless there’s a demonstrated superiority, we don’t want to pay for this expensive drug.” What about the difference in neuropathy? What types of differences would influence a payer to pay for the more expensive drug?

John Fox, MD, MHA: I suspect that if patients develop neurotoxicity on the IV paclitaxel, that would be an indication for covering them. I just want to clarify. As I read the abstract, it looked like in the modified intention-to-treat analysis that the overall survival was 27.9 months versus 16.9 months. Do you think that may be inaccurate because of the study design?

Hope S. Rugo, MD, FASCO: No, I don’t think so. Overall survival is one of those hard end points, so it’s pretty good in general. They have a modified intention-to-treat population, which are patients who took at least a certain amount of drug and is unusual for intention to treat in general. But it was based on the fact of where they did the study and the fact that it was also oral, so I think that is an impressive difference. Of course, survival differences—that’s what you were referring to—might motivate a payer to pay for the more expensive drug.

John Fox, MD, MHA: Yeah. With that said, in practices that are in OCM where the money is coming out of their pockets, what would they do in that circumstance? I think everyone that I know of in the 5 or 6 practices in OCM would err on the side of giving the drug that produced the longest survival. But this study is also interesting because it highlights the importance of doing phase 3 trials. If we were just to have done a phase 2 trial or just looked at progression-free survival [PFS] as an end point, the difference was about a month…between the 2. We would have made a beta-type error and concluded there was no difference when in fact there really was.

I think there are a few frustrations we have as the payers, especially with the 21st Century Cures Act and that the FDA’s approval of a lot of drug is based on phase 2 data alone and often single-arm phase 2 trial data. Our frustration is that we don’t know at the end of the day whether there is a patient meaningful end point that’s been achieved. I think this study’s results showed that it was important to look at overall survival because the difference in PFS was very modest.

Hope S. Rugo, MD, FASCO: I think the neuropathy might also be a way that providers will be able to go back to the payer and say, “I know you want us to use paclitaxel, but this patient already has underlying neuropathy.” It will be interesting because I think that may be very motivating data with the overall survival still relatively early for this trial. Claudine, I know that there has been a question, and Tiffany brought this up a little bit earlier, too, that the control arm wasn’t our standard control arm for this trial with every-3-weeks paclitaxel. How much does that impact your assessment of overall survival versus the neuropathy or other end points?

Claudine J. Isaacs, MD: I think it makes us a little bit less enthusiastic to jump on that huge overall survival benefit. CALGB [Cancer and Leukemia Group B] quite a while ago did a randomized trial looking at weekly versus q3 week [every-3-weeks] paclitaxel and showed that the weekly was superior. I don’t remember the differences off the top of my head, but they weren’t as marked as the differences in overall survival that were seen in this trial.

I think it makes us a little less likely to scream off the rooftops that this is associated with this huge overall survival difference, but it makes you think that it’s unlikely to be inferior and might be a bit superior. There may be a lot of reasons associated with that in terms of how adherent people were or what was going on and what was their access to therapy after. So I think we need to integrate all those things when you’re thinking about survival benefit. I do think we need to be a little cautious to remember that this is not compared with what we would think of as the standard paclitaxel to use in this setting.

Hope S. Rugo, MD, FASCO: I think that that’s an important point, and I think what’s interesting is that in some settings, weekly paclitaxel around the world is not feasible to give, so it’s going to be interesting to see what happens with the further analyses of these data and what people think about them. The issue of more expensive and less expensive will also play a role, as well, in the rest of the world. There are other oral taxanes that are being studied, tesetaxel, which is another type of oral taxane being given in combination with capecitabine versus capecitabine alone.

In the initial trial, which was in patients who’d received taxanes in the adjuvant setting but not in the metastatic setting, of course, and then in another trial, which is going on now in patients who are taxane naïve, so that will be very interesting. That’s an oral agent that’s given every 3 weeks. Then there’s another oral taxane called Liporaxel [oral paclitaxel], which is an emulsion from Korea that’s being tested in a phase 2 trial compared with weekly paclitaxel in the United States now. Priyanka, what are your perspectives on some of these newer studies looking at oral taxanes?

Priyanka Sharma, MD: All these formulations are different in terms of how they’re being delivered, some pills, some emulsions. We do have experience with Liporaxel, which is an emulsion given once a week. It’s liquid that the patient drinks twice a day, and for the most part, it’s relatively well tolerated. The main issues have been with diarrhea and bad taste in mouth. But it doesn’t require the extensive timing of fasting and number of pills. From that aspect, that makes it easier, and you take it only once a week, so there are not multiple doses spread over multiple days. This drug is approved in Korea for gastric cancers. I think we will see more of these agents and formulations, and probably the one with the best efficacy and the one that’s easiest to deliver in clinic might be the winner.

Hope S. Rugo, MD, FASCO: It’s interesting because tesetaxel is being tested in combination with capecitabine, so that’s a little bit different, a little bit harder to separate out the toxicities of that combination therapy. But that first trial, contested trial, has completed accrual, so we hope to see results in the next year or so. Who knows?

It’s interesting. I think we’re entering a new era, where our threshold for thinking that a new drug is good has increased as we’ve had a lot of targeted agents, but I think having oral therapy for us in the United States would be a tremendous advance. We never got the oral vinorelbine approved, so it would be nice to see some additional options for our patients. Thanks very much for everybody’s participation. This was a great discussion.

Transcript Edited for Clarity