Jorge Cortes, MD, discusses the FDA approval of orally disintegrating nilotinib tablets for patients with chronic myeloid leukemia.
Improving upon already-available therapies, like developing an
In an exclusive interview with OncLive®, Cortes discussed how current prescribing information for nilotinib (Tasigna) requires patients to fast for 2 hours prior to and 1 hour after receiving the treatment, an inconvenience patient may no longer need to endure with the approval of the new formulation.2 Moreover, Cortes highlighted how patients who receive the orally disintegrating tablet formulation no longer need to avoid gastric acid–reducing agents like proton pump inhibitors (PPIs). He also noted pharmacokinetic data with the newly approved formulation, in addition to what’s next for the larger CML field.
Cortes is a professor of medicine – hematology and oncology and a senior scientist in the Heersink School of Medicine, chief of Hematology, and deputy director of the O’Neal Comprehensive Cancer Center, all at the University of Alabama at Birmingham.
Cortes: It’s a welcome addition because nilotinib is a good drug. We’ve been using it for many years, and it is generally well tolerated. [Nilotinib] does have the risk of arterial occlusive events, probably the highest among the second-generation TKIs; therefore, it’s not something we use a lot in patients who have comorbidities that put them at risk for arterial occlusive events. But, for other patients, it is generally well tolerated, although it has an element of inconvenience for the patients because they have to administer it twice a day on an empty stomach. [Patients should have] nothing to eat 2 hours prior to, and nothing to eat 1 hour after, [receiving nilotinib]. For the short term, it can be done, but it makes [taking nilotinib] inconvenient.
There are a lot of patients who have irregular schedules because of travel, the way they work, and many other reasons. [These irregularities] many times are what discourage patients either from getting on the drug or from being adherent to the schedule. Eliminating that inconvenience factor makes it more appealing and promotes adherence for patients who could be good candidates for nilotinib. [Orally disintegrating nilotinib tablets] also [are not contraindicated for use with] PPIs that we use for gastritis and ulcers, for example. Many patients need those medications, and being able to co-administer these drugs when needed is also an advantage.
Developing new drugs that advance the field is good, but so is making adjustments to existing drugs that make them more convenient and easier for patients, helping them with their quality of life [QOL]. [The approval of orally disintegrating nilotinib tablets] is valuable, and it helps patients who could benefit from nilotinib by giving them an easier schedule.
Improving Patient QOL and Daily Life With Orally Disintegrating Nilotinib Tablets
Unfortunately, because of our lifestyles and diets, symptoms like dyspepsia are common, and many times you can manage those with just an antacid, but other times you need to use more definitive drugs like PPIs. It is an inconvenience when you cannot use your drug of choice because [the patient needs to take PPIs]. There are drugs that don’t have that interaction, and that’s good, but I always prefer to have all the drugs that are available [at my disposal]. [If taking PPIs] is a limitation, and we have a formulation that eliminates that limitation, it is valuable. It is not an insignificant number of patients who need to be taking PPIs and other similar drugs, therefore, a good number of patients could benefit from that.
The pharmacokinetic data look good. It’s useful to know that [the orally disintegrating formulation] did not significantly change the [bioavailability of the drug when taken with food]. The problem of food with nilotinib has been that it increases [the bioavailability] levels significantly, particularly with fatty food. When the levels do not increase dramatically, you minimize the risk of having toxicities.
It’ll be interesting as we use this drug in the clinic more to see: [Will a lower increase in bioavailability levels] help with the risk of arterial occlusive events? Who knows if some of these arterial occlusive events with nilotinib were not so much because of the drug itself, but because [the bioavailability] levels went up since patients were eating closer to the administration? Having more reliable pharmacokinetics, for any drug, helps efficacy, safety, and adherence.
We are seeing a number of these [novel formulations of existing] drugs coming along, and they’re welcome. These are not game changing in the sense of new drugs that have different mechanisms of action that overcome a different resistance. It’s a different concept: improving on drugs we already have. We’ve always aimed for that. We need to take these drugs for what they are, but within that, it is good to have these drugs that make [treatment] easier for patients.
There are a lot of exciting new drugs coming along with different mechanisms of action. We have a lot of good drugs in CML. It’ll be good to see what [these new drugs] can do and how they fit into our algorithms and [treatment sequencing]. There’s a lot of interest in combinations and good data about the synergy of 2 drugs like myristoyl pocket inhibitors and ATP-competitive drugs. Where does [this combination] fit? What’s the right setting to use [these drugs in]? We’re not going to use combinations in every patient.
[Regarding] treatment-free remissions, we continue trying to get more patients to stop therapy. I struggle about how we reach the ceiling with [the treatment options] we have now. What is the next step to break that treatment-free remission ceiling? We’ve made a lot of progress in CML, but there are still a lot of unanswered questions because [our goal is] no longer about just improving survival. We [have achieved] near normal life expectancy [for many patients], and [now our aim] is about improving survivorship, QOL, daily life, and how we can get patients better and get to a cure.
