Oral paclitaxel yields better outcomes than IV paclitaxel in metastatic breast cancer

Dr Gerardo Umanzor - Hospital del Valle, San Pedro Sula, Honduras

The study we’re presenting is for oral paclitaxel with encequidar. It’s a drug that had two previous clinical trials which were encouraging so it’s a phase III clinical trial comparing it to IV paclitaxel. So it’s the first orally administered paclitaxel drug that is going to be available with positive results.

What methods did you use?

The design of the trial was it’s an open label randomised trial. It’s a two to one: for oral paclitaxel two and one for IV paclitaxel and it’s 205mg/m2 per day for three days and three weeks represents a cycle for the oral, you give it with encequidar. The IV paclitaxel you give it every three weeks which is the label dosing.

We pre-specified a population so we actually have three populations which is the intent to treat population, which includes all the patients that were randomised; you have the modified or pre-specified intent to treat population which were all the patients who got a scan that proved that there was measurable disease and you can compare their response afterwards. Then we have a safety population which were all the patients who received a dosing of either treatment at one point. So it’s a comparison between the oral and the IV direct, face to face.

What were the results that you found?

We’re happy to say that we have positive results. The primary endpoint was for overall response rate which was measured by a blinded and independent clinical radiological centre. It was measuring for partial response or complete response and it was positive. We found a difference which favoured the oral drug. We also have a primary endpoint for safety and tolerability which we’re also glad to say that we had fewer neuropathy side effects which was one of the aims of the study. Also less alopecia which could be important for some patients and a slightly less low grade gastrointestinal that presented more in the oral drug.

For secondary endpoints we had PFS and OS. We have some early results for OS and we’re also happy to say that they are positive and they are also favouring the oral paclitaxel. It’s an improvement in 11 months for almost 27 months for treatment so we’re very happy about that.

Will there be patient benefits as an oral drug?

Definitely because you have to take into account that if you have to have an IV infusion you’re going to have to go to the centre, you’re going to have to find a way to get there. It’s going to be several hours because the infusions usually are at least three hours. So we were talking about it with the patients and it’s basically a whole day that they had to reserve for the IV versus if you take it orally you can take it home. You still have to do the blood test but you can do it locally and you can get the treatment at home which is much more convenient. Less risk of having to have IV needles if you don’t like needles and also less risk for infusion related complications as well which are very important in paclitaxel. So it’s very good benefit. In some places the patients live far away so also if they can take the treatment home it’s a good advantage.

Were there any limitations in the study?

The limitation at first is because it’s a new drug so you always have to go around that. The patients do have to have training because they have to be trained how to take their treatment which is basically so you can ensure that they’re going to take it every day and they’re going to take their dosing. Basically also to tell them that they could either get it orally or IV because it’s randomised. We also had to have the patients come in for lab tests so those are a few hurdles we had to manage but luckily we didn’t have much problem with it. So at the end it worked out well.

What should clinicians using this regimen consider?

We’ve got a lot of experience now because we’ve been using the treatment for the length of the study which has been going on for almost three years. So we know that there are some patients that are going to need support, they’re going to need some blood tests done more frequently, but it’s very independent on the patient. There is no difference, for example, in the risk for neutropenia, they’re quite comparable in the two arms. So it’s getting the feeling of the treatment, getting used to how the patient reacts. It’s what oncologists usually do on a day to day basis because you know that there are some patients that can tolerate it more and other patients can tolerate it a little bit less. So it’s something that you get used to. It’s a learning curve but definitely we have more data so we can give tips or we can give information for the prescribers.

What are the next steps for this study?

For now we’re focussing, or the team is focussing, on getting all the information we can out of this trial because we do have a lot of important data. So the main focus right now is to close that up and get as much information out there, also for the physicians and for the patients to know about the treatment.

Is there anything you’d like to add?

Basically that we’re very excited because it’s a new type of drug. It’s an orally administered drug which oncologists, we’re always looking for new drugs and easy to prescribe drugs, that has a good response. So it’s an active drug that has a good safety profile that is going to take away the fears we have of some of the side effects like neuropathy. Only with that it’s very exciting news to have this type of drug soon, probably, available.