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Dingwei Ye: Hi, UroToday audience. I'm truly honored to be here today on UroToday's platform. As the leading PI of the ARASENS study in China, I'm excited to share with you the recent findings from the Chinese population presented at a recent ESMO Asia conference. Our presentation at ESMO Asia showcased our efforts towards transforming the treatment of MHSPC specifically for the Chinese population.

Now to further explore ARASENS's impact on the Chinese population, let's turn to Alicia's interview with Dr. Zhu Yao. Thank you.

Alicia Morgans: Hi, I'm so pleased to be here today with Professor Zhu, who's the Deputy Executive Director of Urology Surgery at Fudan University Shanghai Cancer Center. Thank you so much for being here with me today, Professor Zhu.

Yao Zhu: Thank you, Alicia, for having me. Nice to meet you.

Alicia Morgans: Nice to meet you too. I'm really excited to speak with you about the ARASENS study and some key findings that you recently discussed that were key findings within the Chinese population. I wonder if you could share some of these findings, especially as they relate to overall survival and development of castration resistance and other key endpoints.

Yao Zhu: Yes, indeed. Yes. In this ESMO Asia meeting, we can see the ARASENS study, they shared the key data from the Chinese population.

The first thing is that there are 202 patients from the mainland of China representing almost one-seventh of the total population. And it is a really multi-region clinical trial with a very diverse patient population.

From the point of view of efficacy, we can see darolutamide combined with ADT plus docetaxel reduced the risk of death by 36% in the Chinese population, which is quite similar to the 32% reduction in the overall population when compared to the placebo and the ADT plus docetaxel and the time to CRPC, time to PSA progression, and the PSA response rates are quite comparable between the Chinese and the overall population.

But there are differences in adverse event rates between the Chinese and the overall population. We can see that the grade 3 and 4 AE is higher in Chinese triplet therapy, 82% higher than 66% in the overall population. Neutropenia is much more common in Chinese with 64% in the triplet arm compared to 34% in the overall population. However, the fibroid neutropenia is much lower at 5.7%. So the incidence of treatment you mentioned associated with AI inhibitor, for example, the fatigue, fracture for and mental impaired disorder, which are lower in the Chinese patients, quite comparable to the overall population.

So we can see the median treatment duration of darolutamide is quite similar in Chinese patients. And overall, however, the percent of Chinese patients requiring docetaxel dose modification was 30% for those who received the triplet treatment, which is higher than 20% in the overall patient population. So we can see there is a quite diverse clinical trial. The efficacy is quite amazing, but there are some difference in the event rates and we should take care with neutropenia in the Chinese triplet therapy arm.

Alicia Morgans: Absolutely. You know I think it is so important that we have specific information around efficacy and adverse events in the Chinese population because of these differences. Because as this comes into China and is being used in the clinical practice, it is important to know what these differences may be despite those adverse events. It did seem that most patients did complete most of the cycles of docetaxel. Was that the case?

Yao Zhu: Yes. We can see after the dose reduction and the dose modification, the overall speaking, the treatment is quite well tolerated in the Chinese patients. And the grade five AEs actually were lower than the overall population. So the clinicians should take care of their patients and the treatment can be very well tolerated in experienced centers.

Alicia Morgans: Absolutely. You know, I wonder if the Chinese population had any other trends or characteristics different from other groups in this study?


Yao Zhu: So this is a very interesting difference between the Chinese and the overall population. We can find a high percentage of de novo metastatic patients in the ARASENS trial. Out of 202 patients in mainland China, only four had recurrent metastatic disease compared to 14% in the overall population. And we can also find a high percentage of Gleason 8 or higher disease along with a higher median PSA value, indicating very high volume tumor characteristics. These observations may be partially due to the lack of PSA screening in China. In my clinical practice, nearly two thirds of my patients are diagnosed with metastatic disease at their diagnosis. So I think it is quite different compared to what happens in the United States. I think these findings commit to some important message. First, the efficacy remains good despite the high-risk disease profile in Chinese patients, especially with high Gleason score and high tumor volume.

And the second point is that the chemo fit criteria require a better definition, considering the trial was conducted in large cities and high volume tumor centers in China and the median age of the enrolled Chinese patients is somehow lower than that of the real world cases in China. So we need more information beyond age and ECOG status to define chemo fit population in China.

And the last point is the cabazitaxel is not commercially available in mainland China, so we should highlight the need to intensify treatment in the castration-sensitive stage.

Alicia Morgans: Absolutely. I think these are such important and key points, especially the point about understanding how this regimen will ultimately get out into the smaller cities and out of the larger organizations that were included in the ARASENS trial. So what specific impact do you think that the results of the ARASENS study will have on clinical practice in China?

Yao Zhu: Yes. So the positive side is that it's quite a large trial and the remarkable survival results with a 12% absolute increase in overall survival and there is really a practice changing trial. I think there is some difficulty to implement the triple treatment in China because the cancer incidence profile is changing rapidly. In the last decade in China, prostate cancer like 20 years ago was ranked the tenth most common male malignancy. And most of the prostate cancer were treated by the urologist, not the medical oncologist.

But nowadays, especially in Shanghai, prostate cancer is ranked as the first most common male malignancy. So the change didn't reflect in the treatment doctors and most of the prostate cancer patients are still treated by the urologist in some small centers and in more broad cities. So we should monitor the docetaxel adverse events and discuss with the patients regarding especially neutropenia, how to adjust the docetaxel dose and how to prevent adverse events. So the education of the physicians and the patients is quite important to implement the advantage of the new treatment approach.

Alicia Morgans: I agree. And what a dramatic change has been happening in China when it comes to prostate cancer in the last few years. That's incredible and a very steep learning curve for everyone, doctors and patients alike. The ARASENS regimen really has been approved in China for nearly a year. I wonder if you have any positive experiences from your practice in Shanghai Cancer Center that you'd want to share?

Yao Zhu: Yes, so in our center, because it's a national cancer center for the treatment and the diagnosis, so we treat a lot of prostate cancer patients and we widely use darolutamide in nmCRPC and the high volume metastatic hormone-sensitive prostate cancer and the response and the tumor control are rapid and impressive because abiraterone is approved earlier in China. When we change the treatment from abiraterone to darolutamide, we can see a significant reduction of the adverse events and also the burden of the doctors. So it's a very nice change.

Alicia Morgans: Well, that's good. I'm glad to hear that. From the ARASENS study, what key points do you think that Chinese doctors and patients should really understand and pay attention to? And I know we've mentioned those adverse events with the docetaxel. Are there those or others that we should pay attention to?

Yao Zhu: Yes. So first of all, I think the ADT alone is not the standard of care in metastasis prostate cancer and the triplet therapy is tolerated in experienced center. And the second point is that the decision about who should receive doublet or triplet treatment is not based on age number, but on performance status, comorbidities and organ function. So this information I think is quite important to spread.

Alicia Morgans: Absolutely. I wonder what are your expectations for the future of darolutamide in China? I think we should acknowledge that ARANOTE and ARASTEP and other studies are coming. What do you think?

Yao Zhu: We are glad there are more steps to try different regimens in the metastatic hormone-sensitive prostate cancer stage. And we are looking forward to a more dynamic treatment approach. For instance, patients may be treated with a doublet for two or three months and then assessed by PSA or next-generation imaging to determine whether to add chemo or not. On the other hand, the patient could receive a triplet treatment and then continue antiandrogens for one or two years. If the PSA is good, they may have intermittent therapy just like the IMPACT trial. So additionally, we need to treat the patients according to their genomic profile like HRD mutation, PTEN loss, and others. I think these attempts are quite interesting to us.

Alicia Morgans: Wonderful. Well, what are the key focus areas for Chinese doctors when they're treating metastatic hormone-sensitive prostate cancer? Anything else you want to focus on here?

Yao Zhu: So I think the first thing is the efficacy. We want to prolong the time to CRPC and have a very nice PSA response. And the second point is we do see those patients with HRD mutation, and PTEN loss, they perform not as good as those patients without specific genomic alteration. So we want to try some targeted therapy in this specific patient subgroup. The third point is that because prostate cancer treatment is a long run, we want to reduce the risk as much as possible. So I think these three arms are the focus we are trying to explore.

Alicia Morgans: I think those are great points. And we didn't mention, but I was really impressed by the number of patients who had a PSA-90 decline as early as 12 weeks in the Chinese population treated. In ARASENS it was very high. So as you say, these are amazing goals and opportunities for our patients to really control their disease. What differences do you see between the current treatment practices in China and those that are happening in Europe or America in this MHSPC setting?

Yao Zhu: Yeah, so the first point, I think there is quite different patient characteristics between China and the West like the US and Europe, because we have different PSA screening policy. In China, there is actually no PSA screen. Patients just refer to the hospital with some symptoms. But PSA screening is widely used in the United States and Europe. So we see more advanced patients with disease. But there is also some difference in the patient among different races.

When we compare the patients, Asian patients in the US with those Caucasian patients in the US, we found still different performance according to the ADT treatment. So I think if we can have more material reading or clinical trial, maybe we have some answer about not only the impact of PSA screening, but also about the race impact on the treatment response. And we are happy to see the nice response of PSA in Chinese patients, and we are continuing to try to explore this Interesting question.

Alicia Morgans: I agree, and I think as we continue to study this combination and others, we will find these differences in efficacy and in adverse events. Even though overall all patients may benefit, there are these nuances and differences that will be so important for us to continue to explore. I wonder as we wrap up, what are the treatment outcomes for prostate cancer patients at Shanghai Cancer Center where you practice?

Yao Zhu: Yes. So there are some reports from The Lancet they have calculated the average five-year survival of prostate cancer cases in mainland China, and they report the median five-year survival is only 66. And in our center, we have increased the rate to 83, but it's still lower compared to the data in the states. But we think the treatment is moving quite fast and we are following the international guidelines and performing a lot of clinical trials, but more efforts should be focusing on the early diagnosis and the treatment of patients at the earliest convenience.

Alicia Morgans: Well, I so appreciate you taking the time to share your expertise, your experience, and the data of the Chinese patients treated within ARASENS with me today. It was truly my pleasure. Thank you so much for your time and your expertise.

Yao Zhu: Thank you for inviting me. Glad to be with you.