Updates on Health-Related Quality-of-Life (HRQoL) analyses in GU Oncology - Cora Sternberg
July 24, 2018
Health-Related Quality-of-Life Analysis From KEYNOTE-045: A Phase III Study of Pembrolizumab Versus Chemotherapy for Previously Treated Advanced Urothelial Cancer
Results from the PROSPER Study: HRQoL Deterioration and Pain Progression in Men with Non-Metastatic Castration-Resistant Prostate Cancer
Cora Sternberg MD, FACP is chief of the Department of Medical Oncology at the San Camillo-Forlanini Hospital in Rome, Italy. She has attained the rank of full Professor of Oncology and is an adjunct professor at La Sapienza University in Rome. She is also adjunct professor of Urology and Urological Oncology at Tufts University School of Medicine and the Lahey Clinic in Boston, Massachusetts, and adjunct professor at Temple University’s College of Science and Technology in Philadelphia, Pennsylvania. A graduate of the University of Pennsylvania undergraduate and medical schools, she completed her fellowship and was on staff at Memorial Sloan Kettering Cancer in NY. Dr. Sternberg is an internationally respected leader in the fields of medical oncology and urological malignancies and a recognized expert in the area of new drug development. She is the principal investigator for numerous studies and an internationally respected researcher who has lectured extensively at universities and cancer symposia worldwide. Dr. Sternberg is particularly known for her influential work in bladder cancer and for her publications on novel therapies for prostate cancer and targeted agents in renal cell carcinoma. Dr. Sternberg has published extensively (more than 375 articles, 6 textbooks) and is an associate editor and editorial board member of several international journals. European School of Oncology (ESO) core faculty and in tune with American medicine, Dr. Sternberg has been elected for a 3-year term to the nominating committee of ASCO’s board of directors.
Alicia Morgans, MD
Read the full video transcript:
Dr. Alicia Morgans: Hi, and welcome to ASCO 2018 coverage. I am so pleased to have here with me today Dr. Cora Sternberg, who is the Director of Medical Oncology at the San Camillo-Forlanini Hospital in Rome, Italy. Just thrilled to have you here to talk today.
Dr. Cora Sternberg: I'm very happy to be here with you.
Dr. Alicia Morgans: Great. I always appreciate your insights and expertise, and there's a lot going on at ASCO this year. You actually have your hands in a lot of things too, and so have a really unique perspective on so many of these things.
Dr. Cora Sternberg: Thank you.
Dr. Alicia Morgans: First, let's talk about urothelial cancer. I know the Keynote 45 study is resulting some quality of life data, which is really important. I think that's the first quality of life data in this particular setting with randomized data. Can you talk to us a little bit about that?
Dr. Cora Sternberg: Exactly. The Keynote 45 trial is the only phase 3 randomized trial with a checkpoint inhibitor, a PD1 inhibitor, that's programmed cell death inhibitor. This is immunotherapy. That has shown in the second line setting in patients with metastatic urothelial cancer who have failed either Cisplatin or Carboplatin, then are randomized. We really had nothing for these patients in second line that was approved. They're randomized between immunotherapy with pembrolizumab versus investigators choice of chemotherapy, which is either docetaxel or paclitaxel or vinflunine in Europe.
That trial showed a 27% reduction in the risk of death per patients randomized to immunotherapy. We have patients that have complete responses. It's really been quite an exciting time for us to have this new kind of therapy in second line.
By the way, there's five new drugs that are checkpoint inhibitors that have been approved by the FDA in second line therapy, but this is the only one with this Phase 3 trial.
What's been published recently are quality of life data. They looked at two different quality of life scores, these are validated scores that are used by the URTC. In those scores that they used, both of them showed that there was no deterioration in quality of life for patients who got immunotherapy as compared to chemotherapy. This is the first time we ever have, in a randomized trial, quality of life data showing with immunotherapy no deterioration in quality of life and improvement in quality of life in patients who got immunotherapy as compared to chemotherapy. I think it's really big news.
Dr. Alicia Morgans: Huge.
Dr. Cora Sternberg: It's really huge, it's really very exciting news.
Dr. Alicia Morgans: Really important to know that our patient can both live longer and feel better and not just ... that's our Gestalt. This is data with validated instruments, like you said, so really exciting.
Dr. Cora Sternberg: Exactly.
Dr. Alicia Morgans: That's not the only thing you're doing at ASCO this time. You're also I think, presenting some data on Radium and creative ways of dosing to try to see if the way that's currently FDA approved is the best way for our patients. What did you do and what did you find?
Dr. Cora Sternberg: Radium 223 has been approved by the FDA and by all of the authorities in the world based upon the ALSYMPCA trial, which showed an improvement in overall survival. Giving six doses of radium, that's 55 kBq is the dosage, and it's given six times, once a month. There were some Phase 2 interesting data showing that giving a higher dose might be better, a higher dose being 88 kBq. Then there was a thought that perhaps if we give the 55 dosage for an extended period of time, for 12 doses, perhaps that could be better too.
The trial was a randomized Phase 2 trial with those three arms, the standard arm of six doses, the 88 kBq doses, and the standard arm for 12 doses. Essentially what we found was that the best is the standard six doses because it was really difficult to give patients the high dose. It was really difficult to give patients the extended dose, and the median number of cycles for all three were six doses, so patients really couldn't get more than the six doses. It just sort of reaffirmed what we knew about from the ALSYMPCA trial. We saw a slightly more toxicity with the 88 kBq with the extended dose, just slightly more, but other than that I really have to say that we need to stick to the six doses and that's about the best that we can do right now. It was an interesting trial to try to do anyway. I'm presenting it at ASCO.
Dr. Alicia Morgans: Absolutely. Wonderful and I look forward to seeing that presentation. I think it's not unusual for patients to say, "I did so well with this the first time around, can I come back for more?" There's been some going up to 12 doses or even just adding a few more doses.
Dr. Cora Sternberg: There was a very small trial by Oliver Sartor.
Dr. Alicia Morgans: Exactly.
Dr. Cora Sternberg: In which he retreated patients with the same six doses, but these were ... just a very small trial, I think it was even published in the Annals, of patients who had been treated and then these were highly selective patients and then treated at another time later on. Maybe you could do that, but we'd need a larger trial to say more about that. That's not what this trial was looking at.
Dr. Alicia Morgans: True, but I think it really helps to shed light on this question and on this issue because many of us said when we saw Oliver's data, highly selective patients who did wait a fair amount of time. These are patients who clearly didn't have cytopenia refractory issues, so again it's just a highly selective population. Is this something that I can apply to my practice and I think that the work that you just contributed is going to be something that really helps to reaffirm, as you said, that the doses that we're giving right now and the series and the sequence that we're giving right now is probably as best we can do for now.
Dr. Cora Sternberg: I agree with you.
Dr. Alicia Morgans: And really helpful.
Great, so thank you. You have your hands in yet another groundbreaking bit of work in the PROSPER Study.
Dr. Cora Sternberg: The PROSPER Study, yeah.
Dr. Alicia Morgans: The quality of life data I think is being discussed at this year's ASCO. I'd love to hear your thoughts.
Dr. Cora Sternberg: I think that the New England Journal of Medicine is finally going to publish today or tomorrow the study.
Dr. Alicia Morgans: Oh wonderful.
Dr. Cora Sternberg: As you said, it was first presented at ASCO GU and then I presented it at EAU. This is a study for patients with a non-metastatic, castration-resistant prostate cancer. Patients who have a rising PSA, but these are high-risk patients. These are patients who have a doubling time of less than ten months, in fact 77% had a doubling time of less than six months. These are patients that are really at high risk. The median doubling time was 3.7 months, if I recall correctly.
In those patients we saw that if you gave enzalutamide ... there is really no treatment for these patients, first of all. There was no treatment for these patients. If you gave enzalutamide as compared to placebo in patients with no metastatic disease by CT scan or technetium bone scan, you get enzalutamide as compared to placebo there was a 71% reduction in the risk of death, of metastases or death. That was really very important. It was metastases-free survival, it was the primary endpoint.
We don't have the overall survival data yet. We should have that in a year or so. We're looking forward to that. The fact that you can reduce the risk of metastases and reduce painful metastases in these patients with bone diseases, this is really correlated with overall survival in the end.
What we have now, that are being presented, we've looked at five different quality of life instruments and we're writing a manuscript on that too. Essentially these are patients that don't have a bad quality of life. They don't have metastatic disease, they have a good quality of life. There's going to be two presentations by Gert Attard is the first author, here at this ASCO meeting. In those, he shows that the quality of life is maintained essentially with enzalutamide and that the quality of life is really correlated with the metastases free survival. There's no real deterioration in quality of life and when there is, it's related to the metastases. I think it's interesting data that's coming out, also again, in terms of quality of life, that's important I think with all the drugs we give, the quality of life is so important.
We're giving a drug to patients that don't have metastatic disease, we want to be sure that we're not hurting these patients either.
Dr. Alicia Morgans: I agree 100% that if we're treating an asymptomatic population it's really critical we think of adding a drug to what they're doing, that we need to understand both what we're doing in terms of disease control and also in terms of quality of life. I commend the study investigators and the study design team for integrating such a robust series of quality of life instruments and I also want to mention that the rate of completion of these instruments was really high. So, patients can do this and we should do this in all of our Phase 3 studies, truly making sure that we understand.
Dr. Cora Sternberg: It's a lot of work, but I think it's really worth it, with the data that comes out.
Dr. Alicia Morgans: I agree.
Dr. Cora Sternberg: Again, these are patients that are not that sick, so they are able to fill out these papers and fill out all of them. When you have a very sick patient population, it's harder to get all the quality of life data that we've gotten here.
Dr. Alicia Morgans: It is, but I think like you said, with support and encouragement from the study team you can get it done. In those patients it may be even more important or important in a different way, I would say, to understand what they're going through. Great job, and thanks again for adding to our understanding of treatment there.
Dr. Cora Sternberg: Thank you.
Dr. Alicia Morgans: Finally, I wanted to touch on a renal cell plenary that's going to be presented. Can you tell us a little bit about this exciting data that we're expecting to hear during ASCO?
Dr. Cora Sternberg: Okay. There were two different actual renal trials that were sort of similar, looking at patients with metastatic disease and whether or not it was important to do the nephrectomy. One of them has already been presented, it was the short time study by the EORTC and there were some problems with accrual on that study. In that study they looked at Sunitinib followed by nephrectomy versus nephrectomy followed by Sunitinib. There was nephrectomy in both arms.
In this study, which is called CARMENA a French trial, so I have not been involved with it. They left out the nephrectomy in one of the arms. One arm has nephrectomy and Sunitinib, these are metastatic patients, and the other arm has Sunitinib alone. I don't know the results yet. If I had to guess I would guess that doing the nephrectomy is useful but I don't really know the results and I'm anxious to go to the plenary session and to hear them, to hear the results.
Dr. Alicia Morgans: We're all very excited to hear that. We'll have to talk with you in the future to hear your thoughts on how we put that into context in our practice.
Dr. Cora Sternberg: Yes, of course.
Dr. Alicia Morgans: What are your closing thoughts or your ideas about ASCO here. It sounds like it's a very busy one for you. Do you have any messages for the listeners?
Dr. Cora Sternberg: I think there's a lot of interesting things that are going to be presented at ASCO. I think that the data on the CARMENA study, it made a plenary session, I think that's the first time a renal study has made plenary session and I think that that will probably be the highlight of it. There are many different things that are very interesting at this year's ASCO, aside from all the meetings and meeting people like you.
Dr. Alicia Morgans: Oh, lovely, thank you. A real year of advances. As usual, many that you have had a hand in, so we appreciate you taking the time.
Dr. Cora Sternberg: Thank you.
Dr. Alicia Morgans: Thank you so much for being here today.
Dr. Cora Sternberg: Thank you very much, it's a pleasure to be here.