Pain and Symptomatic Skeletal Events Reported in the VISION Trial – Oliver Sartor

October 3, 2021

Alicia Morgans and Oliver Sartor discuss additional data from the VISION trial that was recently presented at ESMO 2021.  Dr. Sartor discusses the health-related quality of life findings from the VISON specifically pain and symptomatic skeletal events. Dr. Sartor offers the background on the VISION trial, while also describing the patient cohorts.   Dr. Sartor discusses how the trial patients randomized to the standard of care plus Lutetium-177 PSMA arm are experiencing a significantly longer duration of sustained quality of life before deterioration. The results from the VISON Study demonstrate a positive impact on the patients' quality of life, and that patients on the Lutetium-177 PSMA trial arm are living longer and better lives.


A. Oliver Sartor, MD, Professor of Medicine and Medical Director, Tulane Cancer Center; C. E. and Bernadine Laborde Professor of Cancer Research, New Orleans, Louisiana

Alicia Morgans, MD, MPH Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts.

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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 excited to talk today with a good friend and colleague Dr. Oliver Sartor, who is the Medical Director of The Tulane Cancer Center, as well as being a Professor of Medicine and Urology. Thank you so much for being here with me today, Dr. Sartor.

Oliver Sartor: Thank you, Alicia, glad to be here.

Alicia Morgans: Wonderful. So, I wanted to talk with you a little bit about some additional data that was presented at ESMO from the VISION trial that you and colleagues designed and carried out presented recently at ASCO. This data was really around the health-related quality of life and things like pain and symptomatic skeletal events that impact patients on a day-to-day basis as they are trying to live their lives. Can you tell us a little bit about the VISION trial, who those patients were, and then what you and the team found in terms of the quality of life and the way that they lived during treatment?

Oliver Sartor: So, let's back up just a little bit and talk about, who actually enrolled in the VISION trial. And these were individuals who were very heavily pretreated. The requirements were that everybody would progress after one of the novel hormones, such as abiraterone and enzalutamide. In addition, you had to progress after docetaxel. In truth, Alicia, many of the patients had already gone through two lines of chemotherapy, [inaudible 00:01:22] wound up to two lines of taxanes. About 40% of the patient had had two lines of taxane and another 40% of patients who actually had two lines of novel androgen access inhibitors. So, there really were not a lot of patients that had great options left. Imagine somebody going on abiraterone, enzalutamide, docetaxel, cabazitaxel, and then coming into the trial. And that's, in fact, what happened for a number of these patients. So, very heavily pretreated.

And, of course, just as a reminder, you had to have a PSMA positive pet scan in order to get into the study. But about 87% of the patients who did have a PSMA pet actually were able to enroll in the study.  And then randomized versus standard of care as compared to standard of care plus the PSMA lutetium. So, that's the basic design. We had already discussed and had reported in the New England Journal the overall survival benefit, hazard ratio of 0.62, and the rPFS hazard ratio of 0.4. Here, what we have is some of the newer data on the FACT-P time to deterioration and also the symptomatic skeletal events, as you mentioned, and also some of the data on the time to pain deterioration. And maybe I'll just stop there and kind of let you probe where you wanted to go, but that's the overall design and kind of what the new data might be available now.

Alicia Morgans: Thanks. And I just want to emphasize to everyone that I think it's so important to use this data in combination with the rPFS and OS data that you've already presented, because the comment has been made, maybe this median improvement in overall survival of four months is not necessarily doing much for us. But I think that the story is much broader than that because certainly, some patients had a much longer time because of course that was the median. But living life is not the only thing. Patients want to live life without pain, and they want to be able to do the things that they want to do. They want to see the people that they care about. They don't want to be hospitalized for skeletal events. So, let's start with the FACT-P which is really helping us understand the overall quality of life, sort of a composite type score. How did the arms do in terms of that overall quality of life?

Oliver Sartor: Well, I think it did quite well. So, we will look at things in a comparative sense. Remember these are heavily pretreated patients and in the control arm, deterioration in the quality of life was 2.4 months. So, guess what? People didn't do very well if they were on the control arm. It was actually almost 10 months, 9.7 months for time to deterioration in the experimental arm, those treated with PSMA lutetium. That is a big difference, going from 2.4 to 9.7 and the hazard ratio was... oh gosh, I have to refresh my memory for a second, but I think it was 0.46 if I look over here at my cheat sheet. So, this is a very substantial difference in the medians, a very substantial difference in the hazard ratio, and tells us that people were able to maintain their quality of life for a longer period of time, which is an immensely important measure when you're talking about the effectiveness of cancer therapy.

Alicia Morgans: Absolutely. And that FACT-P includes things like physical functioning, emotional functioning, even things like social functioning, how you are able to engage in those activities you normally do, and of course, prostate cancer-specific concerns. So, great that there was such a pronounced prolongation in the maintenance of that overall quality of life. One of the most important things to patients from what I can understand though, in some qualitative data, and of course in our clinic is really making sure that patients do not have pain. So, can you tell us a little bit about the pain data? Because I think that is some of the most impressive.

Oliver Sartor: It was impressive to me. So, time to pain deterioration is a really important measure because people who were able to maintain their status with regard to pain in an ongoing manner are really able to function better. And I think that is reflecting the overall FACT-P, but actually came out over 14 months for time to pain deterioration. And, you can talk about the rPFS, but it didn't really capture the impact on patients' lives. So, over 14 months in these heavily, heavily, heavily pretreated patients to be able to maintain an absence of pain deterioration, I think is quite impressive as compared by the way of the control group to 2.9. So, huge difference, over 14 months, 2.9 in the two groups. And I think that is a very, very important measure of how people are actually benefiting from the drug.

Alicia Morgans: I would agree, and to remind everybody, of course, these are patient-reported outcomes. So, these are the outcomes that the men who have prostate cancer dealing with these symptoms, it is data from them. It is not data that's really filtered through the physician or the clinical team at all. And so, I think that is another part of it that makes it so important, as patients themselves are trying to choose what to do next. So, you also included in this analysis, symptomatic skeletal events, of course, those events that are noticed by the patient and were not just picked up on routine scans. So, tell us a little bit about the SSE data.

Oliver Sartor: Well, it cut the SSE rate in half. The hazard ratio is 0.5. So, literally the risk of radiation to bone, fractures related to cancer, pathologic fractures, spinal cord compression, and procedures related to bone. All these clinically relevant events were cut in half. And again, I think that is very, very impressive. We talked about that benefit with such things as denosumab, zoledronic acid, radium-223, and the initial ALSYMPCA trial showing benefits in SSE. That is a very impressive difference in SSE between the control group and the experimental group, cutting the rate in half.

Alicia Morgans: So, important too, because we know these symptomatic skeletal events can really immobilize patients causing incredible morbidity and also increasing the chance of mortality. So, really, really an important endpoint as well.

Oliver Sartor: And one of the things and I think Bertrand Tombal and Silke Gillesson and people have emphasized is the degree to which the bone health agents are important from their recent data from PEACE III. And then, of course, people like Fred Saad have long been preaching this. Karim Fizazi has long been telling us about these stories. But the use of bone health-protective agents, I think is important for these patients. And I hate to say it, even as experienced physicians, sometimes I kind of lose track a little bit, and it's embarrassing if somebody is not on a bone health agent, and then they get a compression fracture that leads to debilitating pain. Now that's... unfortunately that is not the best medicine and we need to keep reminding people, these are important auxiliary elements to the care of the patients in advanced prostate cancer.

Alicia Morgans: I could not agree more and trying to put systems into our programs that help remind us or help automate the reminders about bone protective agents is one of the things that I'm hoping that we can all do over time. Because it is really hard to remember when we are so focused on the disease and controlling prostate cancer, sometimes that aspect of care does fall by the wayside. We definitely need to pay attention to it. So, as you think about this data, which I think is some of the most important to come out of VISION after the initial survival in rPFS data, what would your summary be?

Oliver Sartor: People not only live longer, but they also live better. And the time to deterioration is clearly improved. And the time to pain, as being a problematic issue, is also very substantially improved. Remember, to me, it's in the comparison, we are talking about 2.9 to over 14 months of pain control with this particular agent, that is a rather remarkable difference in these far advanced patients.

Alicia Morgans: I could not agree more. I really appreciate the work that you and the team have done. Certainly appreciate the patients who participated. And thank you for taking the time to talk with me about your ESMO presentation today. Thanks so much, Dr. Sartor.

Oliver Sartor: Thank you, Alicia. My pleasure.