Alicia Morgans: Hi. I am thrilled to have here with me today, Dr. Darren Poon, who is a consultant in Clinical Oncology at the Chinese University of Hong Kong. Thank you so much for coming today.

Darren Poon: Thank you for having me and it's my honor to be invited.

Alicia Morgans: Of course. Well, I am excited to meet you today at APCCC 2019. You gave a really, I think, clinically relevant talk, but a talk that we have not discussed actually widely, at least in the United States. It's something that we just don't always think about, I think. It's pharmaco-ethnicities specifically as it relates to drug toxicities in Asian patients. And I'd love for you to explain that concept a little bit to us and help us understand, why is it important to think about?

Darren Poon: Yeah, because we have some observations about some shortcomings about the clinical trials that we have already been done in the last 10 to 20 years about prostate cancer because we have observed that the participations of non-Caucasian populations, especially from Asian population is quite limited among different pivotal studies. So say for example, this by Asian constitute around 60% of human populations. There's only less than 10% of clinical trial participants where come from Asia.

There was some problem with that because some of the data will be missing in particular with the tolerability and efficacy because there may be some diversity in terms of these aspects between Caucasian and Asians. And we do have observe some real world data about the tolerance with the cytotoxic treatments in prostate cancer patients, especially in Asian populations. We, from our Bureau data, we have observed a high incidence of modest oppressions with taxane chemotherapy for the metastatic prostate cancer patients.

Irrespective of the status, including both [inaudible] and mCRPC patients. Say for example for our data, around 50% of them had developed febrile neutropenia, such a radius remarkably high compared to the pivotal studies differ somewhat from CHAARTED. It's only 6% from the texts 3% to 7%, is only 3% to 5%, so you can see there's a huge difference in terms of the tolerability for cytotoxic treatments.

Although we have some data about the efficacy for these life-prolonging therapy is suggested that there is no obvious difference, but the tolerability will be much different between Caucasian and Asians. But these data has not been well addressed in the clinical trials that have been published or released in the meeting. So we look forward for more data about the pharmaco-ethnicity in the clinical trials because a more precise result and with a more specific result and specific dosing of treatments, maybe how to improve the tolerability in Asian populations. But then I've tried to maintain a good efficacy with these agents. So we look forward for more data in the near future. Yeah.

Alicia Morgans: Absolutely. So I think that's exceedingly striking that there was a nearly 50% febrile neutropenia rate in an Asian population. And there are two things that I want to really emphasize there. One, it was real world data, so these are the patients that you see in clinic every day and many of the patients that I probably see in clinic as well, and it's, yes it is different than a clinical trial population where there are lower rates perhaps, but that is in an ideal situation and those are not reflective. Those patients are not necessarily reflective of the majority of patients that we see in our practice.

The power of that real world data is enormous when I'm trying to use that concept in my clinical practice. And the second thing that we talked about actually a few minutes before we started recording was that with this febrile neutropenia rate, you and your team are probably using more Neupogen® or Neulasta® or growth factor support in your practices, and that I think is pretty easy for us to integrate into our practices here in the United States. If we are seeing patients who are Asian patients, to think about that, maybe say I'm not going to do it for one reason or the other, but really to think about growth factors a little bit differently in an Asian population perhaps they need a little more support for their marrow if they're going to be getting cytotoxic therapy and that's an easy enough switch for most of us to make.

Darren Poon: Yeah, absolutely right. Yeah. The use of a primary G-CSF is not that popular for a prostate cancer patient in States or in Canada, but in Asian we are tried to getting, I mean the advocation of using more primary G-CSF in our patients in view of the high incidence of a febrile neutropenia for patients with a taxane chemotherapy. And you know, despite we have a lot of choices in the mHSPC setting, we have chemo, we have AR agents, but still, chemotherapy will be a major weapons for mHSPC patients. We don't want to deprive the clinical benefit of chemotherapy in mHSPC patient in an Asian population, simply because of the poor tolerability to chemotherapy.

We try to keep the patients can tolerate the chemotherapy and there are two ways to do it. The first way, as we have mentioned, by the use of a G-CSF and the second way we can try to modify the dose of chemotherapies. Say, for example, it's a common clinical practice in Asia, in particular in Japan, they will start the patients with a lower dose of docetaxel. For a standard dose, it will be 75 milligram per meter squared. But in Japan, they would start the patient with a 60 milligram per meter square. And the risk of having febrile neutropenia or mild suppression will be lower compared to coming off using a standard dose of chemotherapy. That will be another way to reduce the risk of having mild suppression with taxane in Asia.

And the second way we've mentioned is the primary use of G-CSF. It has been demonstrated by some prospective study even in the situation with cabazitaxel. There's a recently published paper showing that other use of primary G-CSF in patients with cabazitaxel the risk of having febrile neutropenia will drop from 50% to 9%, so that highlights the value of using primary G-CSF in Asian populations with taxane treatments.

Alicia Morgans: Wonderful. So I think a couple of other points then just to emphasize that we would not want patients to not have the opportunity to get these therapies. That's certainly not the message, but that we need to support them perhaps a little differently as we use these treatments. And before we wrap up, are there differences in the AR targeted therapies in terms of efficacy or tolerability that you found in your data?

Darren Poon: That's a different story from chemotherapy based on the ... I mean both prospective studies and some real world data. We find that the efficacy is basically similar in Asian patients compared to the pivotal studies of Caucasian samples. And regarding the toxicity of an AR agent is quite similar to the efficacy that there's not much difference in terms of the efficacy between Asian and Caucasians.

Say for example within a separate analysis that primarily focus on East Asian ethnicity within the peripheral trial, the hazard ratio is basically similar, I mean the survival has a ratio that's basically similar between East Asian ethnicity and a global result, so in terms of the tolerability or the efficacy with AR agents is a little bit similar between the Caucasian and Asians. It's a little bit different from chemo. Efficacy would be the same, but the tolerability with the chemotherapy, it may be poor. In Asian public, we don't know the exact reason for the poor tolerability with chemotherapy properly. It may be due to the body size because you know the body size or the body build will be much different from Asian and Caucasians and then the marrow reserve will be also different. Asian population will have a limited marrow reserve and then the susceptibility to the massive pressure with chemo will be higher. So that may explain why more people would get febrile neutropenia with chemotherapy, but that's not to say it starts already with AR agents.

Alicia Morgans: Interesting and really important to note, too, so it doesn't really seem to be the case with AR agents. So I really appreciate you taking the time to speak with me today. I think that everyone will have learned a lot and at a minimum, I think that as we're seeing men with prostate cancer who are of East Asian ancestry, we should ensure that we're thinking about growth factor support, if not dose reduction, and that's all of certainly at the discretion of the clinician taking care of that patient. But from a safety perspective, like I said, I think that it's not hard to integrate a growth factor support and think about dose reduction, particularly if people are older, frailer or smaller. Like you said, the habitus, the body habitus may play a role. So thank you so much for your time.

Darren Poon: Thank you for having me. It's my pleasure to talk with you. Thank you very much.

Alicia Morgans: Thank you.