John L. Fox, MD: In general, there are a number of factors that we consider when making formulary decisions. First is certainly the rarity of the condition, and in rare conditions like ovarian cancer where the cost is going to be relatively minimal compared to other conditions, that might influence us not to manage that category. But certainly, we look at other factors. We look at the opportunity for misuse, abuse, or overuse of a therapy. In cancer, in general, there’s typically not overuse. Although, there may be some misuse because providers are using things out of the appropriate sequence in the line of therapy or are using the therapy too long after the patient has progressed because there are no alternatives available. We certainly look at cost-effectiveness. If there are multiple drugs that have a similar mechanism of action and have similar outcomes, we’re going to look at what the relative cost difference is for those and choose the one that’s most cost-effective. Having said that, in rare conditions the relative cost may be large, but the overall cost may be small. Again, that will influence our decision about whether or not we want to actively manage that category.
One challenge for health plans is, when drugs are similarly priced, what do we look at after that? Typically, we look at efficacy and safety and then price. If we have therapies that are comparably priced, efficacy is probably the most important factor. The challenge, though, especially with the PARP inhibitors, is that all 3 PARP inhibitors were approved based on preliminary data, given accelerated approval based on overall response or on progression-free survival. There is a significant challenge, even more so in this space, because of the preliminary data and the challenge in looking at indirect comparisons.
Complicating that even further is that the populations studied were not comparable. Some studies were looking at BRCA-mutation positive disease and others at loss of heterozygosity. Some were looking at first-line, second-line, or third-line therapy, and so the ability to make indirect comparisons is very challenging. While the prices may be the same, the indications may be different. Frankly, as a health plan, until proven otherwise, we believe there’s likely to be a class effect. We may decide that we’re going to manage these drugs after patients failed their initial platinum-based therapy and allow access to any therapy, but choose the ones that are most cost-effective.
While health plans may simply choose to allow a PARP inhibitor in any line of therapy after a platinum-based therapy, they also may look at the breadth of the indication for a single agent and say, “This agent has the most indications: second-line, third-line, BRCA-mutation positive, BRCA-mutation negative, LOH (loss of heterozygosity) positive and negative.” The drug that has the greatest number of indications has the greater likelihood of being covered, but that depends on the physician as well. We may say we’ll allow coverage for any indication, and if the physician wants to use something beyond the FDA label or beyond study if they believe that’s the most effective therapy for that patient, we may allow that. But again, having more indications gives you a greater likelihood of getting covered than having narrow indications.
An interesting question now that we have new therapies available, including Avastin and PARP inhibitors, is what to do about maintenance therapy. Interestingly, with the combination of platinum-based therapy with a taxane, we haven’t done maintenance therapy because of the associated toxicities. Typically, you would give 6 cycles of therapy and then stop, wait until the patient developed symptoms, and then retreat in a platinum-sensitive patient. But now that we have alternate therapies available that have fewer toxicities, the question is, what do you do about maintenance?
I think the reality is the data show that in patients who have platinum-sensitive disease and recurrence of their disease, you can treat with a platinum-based therapy along with Avastin, stop the platinum-based therapy, and continue the Avastin until the patient progresses. Likewise, there are studies that show you can continue the PARP inhibitor if you’re using that as a second- or third-line therapy until the patient progresses. And then, the third instance is where you can treat a patient with a platinum-based therapy and then go into maintenance with a PARP inhibitor. So, as long as the evidence shows that there is an advantage to that progression, it will be a covered service.