At ASCO the OPTIMAL trial was presented. The OPTIMAL trial is a phase III study evaluating oral paclitaxel versus IV paclitaxel in HER2-negative metastatic breast cancer. Paclitaxel is a cornerstone in the management of breast cancer but it is solubilisable by Cremophor, it is associated with a high percentage of reactions in peripheral neuropathy and requires infusion time. Three-weekly versus weekly showed that the weekly regimen has a higher efficacy but because a weekly regimen means more frequent hospital visits. So our hypothesis was that if the oral paclitaxel is an alternative comparable to the IV paclitaxel it can reduce not only the medical course and the hospital visits, it can overcome the disadvantages of IV paclitaxel.

Before we conducted this trial the oral paclitaxel has an advantage: free from the Cremophor EL and also no need for p-glycoprotein. A phase III study was conducted in gastric cancer, it was approved in Korea and Japan, and also before we conducted a phase III trial, the phase II trial demonstrated that the progression free survival was 8.9 months and overall response rate is 50% in this population and acceptable toxicities. Based on the previous research, this is the rationale to proceed into a phase III study.

What was the methodology and what did you find?

This is a non-inferior design so the relative margin is 1.33. The primary endpoint is progression free survival for oral paclitaxel versus IV paclitaxel. That hazard ratio crosses 1.0, the upper limit of the confidence interval did not exceed 1.33 which means it is non-inferior, almost comparable. Also the overall survival data, response rate data and toxicity profile were almost comparable although hematologic toxicity, neutropenia, thrombocytopenia and anaemia were more common and also GI toxicity – diarrhoea, nausea, vomiting – is more common in the oral form but it is usually grade 1 and 2, it is manageable. But peripheral neuropathy, hyposensitive reaction, infusion-related reaction, is more common in the IV paclitaxel.

So based on this comparable efficacy, the acceptable toxicity, this oral paclitaxel, DHP107, could be an alternative to IV paclitaxel in the management of the HER2 negative chemo-naïve patient population. If it is applicable in the clinical setting it can reduce the medical costs, administrative costs, it can reduce the hospital visits, it can overcome the disadvantages of IV paclitaxel.

Is there anything else you would like to add?

Oral paclitaxel, I mentioned that it has a definite advantage but nowadays paclitaxel is an important partner with the immune checkpoint inhibitors. So without the steroid it’s an advantage of this oral paclitaxel. And also safety is an issue so it can move to oral and also a good combination pattern with the immune checkpoint inhibitor. So it has more chance to expand further.