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Alicia Morgans: Hi, my name is Alicia Morgans, and I'm a GU Medical Oncologist at Dana-Farber Cancer Institute in Boston. I'm so delighted to have here with me today, Dr. Karim Fizazi, who is a Professor of Oncology and a GU Medical Oncologist at Gustave Roussy, in Paris. Thank you so much for being here with me today, Dr. Fizazi.

Karim Fizazi: Thank you very much, Dr. Morgans.

Alicia Morgans: Wonderful. I wanted to speak with you a little bit today about some really important data from the VISION trial, in which patients reported their own health-related quality of life, and you were able to compare between the arms, and have some data to share on that today. Can you tell us a little bit about VISION and what you and the team studied?

Karim Fizazi: Sure. So, VISION is a large phase three trial, which was the first trial to randomly assess, as a phase three at least, randomly assess the role of PSMA lutetium in men with metastatic castration-resistant prostate cancer. Those men had to have progressed after at least one next-generation hormonal agent, such as abiraterone or enzalutamide, and also at least one taxane, docetaxel, if not two, including cabazitaxel. So these patients with obviously not many options to remain were randomized to receive either standard of care, which was basically whatever you wanted unless there was an issue with the combination with the experimental drug, which was lutetium PSMA, or the combination of the two treatments.

At ASCO this year, we saw the first data for the co-primary endpoints of radiographic progression-free survival and overall survival, and actually, both were significantly improved with a hazard ratio of 0.4 and 0.6, respectively, which is obviously fantastic [inaudible 00:01:54] validations. So what we just reported here at ESMO, was the data regarding quality of life, pain, and skeletal-related events, which obviously are very important on top of overall survival. And here again, the news is good, I think, or great because what we saw in terms of quality of life, assessing the FACT-P total scores was that PSMA lutetium really postpones the time to worsening with a hazard ratio of 0.46.  When it comes to medians, we saw approximately two months versus approximately 10 months in the experimental arm showing you the big difference that we saw and the same Delta actually applied to what we saw in terms of pain.  In terms of deterioration in pain intensity using the BPI questionnaire, the median was three months in the control arm versus approximately 14 months in the experimental arm. So big, big difference, clearly favoring the Lutetium PSMA arm.

Alicia Morgans: So I think that is so important to emphasize if it takes nearly a year longer for a patient to have pain progression. From my perspective, that is probably one of the most valuable things that a patient is looking for. And certainly when we looked at the median improvement in overall survival in this heavily pretreated population, that four-month improvement is of value, knowing that some patients probably had much longer than that, that was a median, but the pain progression also, I think is extremely valuable. What would your thoughts be on that and in your practice, is that something that patients are looking for?

Karim Fizazi: Oh, clearly. Yes. I mean, many of these men are symptomatic or will soon become symptomatic, and postponing symptoms, keeping them with good quality of life for months is obviously very important, on top of the overall survival benefit. Another way to look at this data, of course, is to objectively assess the time to first symptomatic skeletal events. And this is also something that we did in VISION and here again, we saw a significant difference favoring the Lutetium PSMA arm, the [inaudible 00:04:26] reduction was approximately by half, the hazard ratio was 0.5 and the median time to symptomatic skeletal events was approximately seven months in the control arm and approximately one year in the experimental arm. So again, this is really showing you that not only are we postponing deaths, but also we are prolonging good life or good quality of life for all the patients, which is key, of course, in those very advanced situations.

Alicia Morgans: Absolutely. And these symptomatic skeletal events can be associated with extreme declines in function, and of course, are associated themselves with increased mortality. So prolonging the time until those events or preventing them if we can, is critically important to our patients. So, if you had to summarize this data related to the safety, the quality of life, and the way that men actually are experiencing their lives during treatment or after treatment even, with Lutetium PSMA, what would that be?

Karim Fizazi: I would say just in one sentence that, we now have evidence for one last optional treatment, because this was really the concept of VISION and this is obviously lutetium PSMA. And this is based on evidence that life is prolonged, progression-free survival is also improved, quality of life is improved, symptomatic skeletal events are delayed, as well as the duration in pain. And generally speaking, the toxicity pattern is very acceptable.  Many men would report some mild dry mouth, but you know, not really alarming them. I have to say, they still keep the taste and you need, of course, to be cautious with the hematological toxicity, but usually, it is a well-tolerated treatment.

So I think this is now ready to be launched, hopefully very soon in many countries as a routine treatment for these patients with advanced disease. And there are many questions about PSMA lutetium and PSMA targeting in general. Hopefully, we will soon have more trials to address those questions. Of course, one important is whether using these agents earlier makes even a greater difference as we saw with chemotherapy or with hormonal agents. But of course, we have to enroll all the patients to have the answer now.

Alicia Morgans: I would completely agree. And I also agree with your summary that this is a reasonable option when approved, if approved at some point in the future in patients who are heavily pretreated and are basically in the last line, in terms of their metastatic CRPC. But we all look forward to a day when that approval could be a little broader and perhaps we can use it earlier, like other agents, and get some more bang for our buck. But an important first step, nonetheless. So, thank you so much for taking the time to go through all of this. And thank you and your team as well as the patients for the work on VISION.

Karim Fizazi: Thank you very much.