RAPSON Trial Explores Radium223 and Docetaxel Sequencing in mCRPC - Vincenza Conteduca
September 26, 2024
Vincenza Conteduca discusses the RAPSON trial, which compares treatment sequencing of radium-223 and docetaxel in metastatic castration-resistant prostate cancer (mCRPC) patients who have progressed on androgen receptor pathway inhibitors. Dr. Conteduca discusses the trial design, which randomizes patients to receive either radium-223 followed by docetaxel or vice versa. The primary endpoint is change in quality of life, with secondary endpoints including progression-free survival and overall survival. Preliminary results show improved quality of life and tolerability in the radium-223 first arm, with no significant differences in survival outcomes between the two sequences. Dr. Conteduca emphasizes the importance of focusing on quality of life in mCRPC treatment, given the extended survival times achieved with modern therapies. The study aims to provide insights into optimal treatment sequencing for this patient population.
Biographies:
Vincenza Conteduca, MD, PhD, Associate Professor, Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
Neeraj Agarwal, MD, FASCO, Professor, Presidential Endowed Chair of Cancer Research, Director GU Program, and the Center of Investigational Therapeutics (CIT), Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Biographies:
Vincenza Conteduca, MD, PhD, Associate Professor, Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
Neeraj Agarwal, MD, FASCO, Professor, Presidential Endowed Chair of Cancer Research, Director GU Program, and the Center of Investigational Therapeutics (CIT), Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Related Content:
ESMO 2024: RAPSON: Open-Label, Multicenter Randomized Trial of Radium-223 -> Docetaxel Versus Docetaxel -> Radium-223 Sequence in mCRPC with Prospective Biomarker Evaluation
ESMO 2024: Invited Discussant: RAPSON: Open-Label, Multicenter Randomized Trial of Radium-223 and Adding Metformin to ADT for Patients with mHSPC
ESMO 2024: Are Cytotoxics Still the Next Option?
ESMO 2024: RAPSON: Open-Label, Multicenter Randomized Trial of Radium-223 -> Docetaxel Versus Docetaxel -> Radium-223 Sequence in mCRPC with Prospective Biomarker Evaluation
ESMO 2024: Invited Discussant: RAPSON: Open-Label, Multicenter Randomized Trial of Radium-223 and Adding Metformin to ADT for Patients with mHSPC
ESMO 2024: Are Cytotoxics Still the Next Option?
Read the Full Video Transcript
Neeraj Agarwal: Welcome to UroToday. Today we have our special guest, Dr. Vincenza Conteduca, an Associate Professor at the University of Foggia in Italy. She will be discussing with us her recent presentation at the ESMO 2024 meeting on sequencing of radium followed by docetaxel or docetaxel followed by radium in patients with metastatic castration-resistant prostate cancer. Dr. Conteduca, thank you very much for joining us today. Would you be able to please tell us about your research and presentation at the ESMO meeting?
Vincenza Conteduca: Thank you very much for your introduction. I'm very happy to be here today and to share my preliminary data from the RAPSON trial that I presented at the ESMO 2024, so just one week ago.
This is an open-label, multicenter randomized trial of treatment sequencing between radium-223 and docetaxel in mCRPC patients. One of the most important questions for developing my trial is: For patients progressing on androgen receptor pathway inhibitors, is docetaxel or radium-223 the preferred choice? This is a very important question, particularly after some trials presented before during the ESMO conference—for example, PEACE-3 in evaluating the combination between enzalutamide plus radium-223 in patients that didn't get before androgen receptor pathway inhibitors.
Based on this key question, in 2015, I developed this RAPSON study including patients affected with symptomatic bone-dominant mCRPC progressing after any ADT, abiraterone, and/or enzalutamide. These patients were randomized 1:1 into two arms. In the first arm, patients received radium-223 and then, at progression, docetaxel. In the second arm, patients received docetaxel and then, at progression, radium-223. The step two is optional according to the clinical evolution of disease, including the onset of visceral metastasis or poor clinical conditions.
The primary endpoint of the RAPSON trial is a change in quality of life. Secondary endpoints are progression-free survival, total progression-free survival, overall survival, safety, and the identification of biomarkers. In patients receiving radium-223, the assessment of a patient's bone status is mandatory, and particularly they usually receive bone-targeting drugs to avoid fractures. The sample size of this study is 70 patients. We had no stratification factors.
For the assessment of quality of life in this trial, we use two different scores: FACT-P score and Bone Pain Inventory for bone pain intensity. We perform these two scores at different time points of the trial—so at baseline, during treatment, and at progression. One of the most important time points is 12 weeks, representing one of the most important timings for evaluating the change of quality of life in our patients.
Let's start with some preliminary clinical data from this trial, particularly quality of life. We can see a change in FACT-P quality of life score from baseline to week 12. In particular, we observe a deterioration in quality of life from baseline to week 12 in patients receiving docetaxel compared to patients receiving radium-223. Then we perform quality of life analysis within each treatment arm. So we can see a significant worsening in quality of life within only the docetaxel arm between baseline and 12-week evaluation. We can see this significant difference in quality of life from baseline and 12 weeks in patients receiving radium-223.
In addition, we perform a responder analysis only for bone pain intensity. A responder analysis showed a higher incidence of responders in terms of pain intensity and its interference with daily activity in radium-223 patients versus docetaxel-treated patients. In addition, we look at the quality of life in terms of tolerability, and so we checked for the treatment discontinuation rates in the docetaxel arm and within the radium-223 arm. We found a higher treatment discontinuation rate in patients receiving docetaxel compared to patients receiving radium-223. In fact, we observed seven treatment discontinuations in the docetaxel arm versus two treatment discontinuations in the radium-223 arm.
In addition, we perform a survival analysis, but I would like to better specify that the survival analysis is just a secondary endpoint of this trial, and in particular we look at the progression-free survival and overall survival. So far, they are just preliminary data, but in my opinion, they are a bit interesting.
In patients receiving radium-223, we observed a progression-free survival of 7.3 months compared to patients receiving docetaxel with a PFS of 9.7 months. We didn't obtain a significant difference between these two arms. In addition, we look at the overall survival. It was not reached in patients receiving radium-223, and it was 17.4 months in patients receiving docetaxel with a p-value of 0.964. So we didn't observe any significant difference between these two arms.
Based on this preliminary data, we can say in conclusion that the RAPSON trial provided preliminary evidence to support the use of radium-223 prior to chemotherapy in bone-dominant symptomatic mCRPC patients with clinical benefits in terms of better quality of life and tolerability. We observe no treatment differences in PFS and OS between the two treatment sequence arms, but additional follow-up and ongoing identification of outcome predictors might allow a more personalized approach to this sequential therapy strategy in mCRPC patients.
Neeraj Agarwal: Thank you very much. That was wonderful, and congratulations again for doing this very pertinent study looking at the sequencing of radium-223 followed by docetaxel or docetaxel followed by radium-223. So, Dr. Conteduca, if I want to summarize this for our audience, it looks like you took patients who had bone-predominant metastasis, they had symptomatic mCRPC, and when you treat them with radium followed by docetaxel or docetaxel followed by radium, it seems like the secondary outcomes of survivals, PFS or OS, they remain similar in both arms. But patients seem to have maintained a better quality of life as far as radium followed by docetaxel was concerned. Is that correct?
Vincenza Conteduca: Yes.
Neeraj Agarwal: Okay.
Vincenza Conteduca: That is a good question. This is a nice topic because it is, in my opinion, very interesting, especially so far because we have several available drugs for mCRPC patients, but we use a lot of these drugs in every stage of disease, like metastatic—for example, metastatic hormone-sensitive prostate cancer. So when we arrive in the mCRPC setting, we need to know exactly what is the best strategy for our patients. Probably I think quality of life as a primary endpoint is one of the most important aspects that we have to consider in our patients because we prolong a lot the survival in these patients thanks to new drugs. But we need to know what is the exactly better tolerated treatment sequence in our patients. I think the quality of life as a primary endpoint is challenging, but I think is innovative, especially is very helpful for our patients.
You're right, I show preliminary data on survival, PFS, OS. They are interesting, but I would like to underline that they are just secondary endpoints because they are preliminary data. We have a few patients with ongoing treatments, so we need to have the update of this data, probably next ESMO. I don't know for the next ESMO Conference, but they look great because if we don't have differences in terms of survival, I think the primary endpoint is quality of life is our best choice for our patients.
Neeraj Agarwal: That's wonderful. Thank you so much. So it looks like in the context of the PEACE-3 presentation, which was presented by Dr. Gillessen and team at the ESMO meeting, we have a choice of using radium plus enzalutamide. The survival outcomes were quite striking, both PFS and OS, and now we have these data which support good quality of life or at least quality of life seems to be better with radium followed by docetaxel chemotherapy. How do you see yourself sequencing in your clinic moving forward, assuming both drugs are available?
Vincenza Conteduca: Yeah, this is a good question, and I think all these studies that you mentioned are the background of my study because my study is just a Phase 2 trial.
Neeraj Agarwal: Yeah.
Vincenza Conteduca: So you mentioned ALSYMPCA and the PEACE-3 study that have Phase 3. I think my study, it's a small role, but it's very important because it included just a subset of patients progressing on ADT, enzalutamide, and abiraterone. So it's a different setting from PEACE-3 and in particular from the ALSYMPCA trial. The RAPSON trial has a different endpoint because it aims to assess the best treatment sequencing, so not just the role of radium-223. We have some patients progressing after docetaxel, but also prior to chemotherapy disease. It's very challenging to give radium-223 before docetaxel even also after androgen receptor pathway inhibitors. So I think probably the RAPSON trial could represent an aspect in the overall management of mCRPC patients.
Neeraj Agarwal: Thank you very much. So that concludes our discussion. I'd like to thank again on behalf of our viewers, Dr. Vincenza Conteduca, for taking the time to join us today. Thank you.
Vincenza Conteduca: Thank you for this opportunity to share this data, and I'm happy to update my data very soon. Thank you very much.
Neeraj Agarwal: Welcome to UroToday. Today we have our special guest, Dr. Vincenza Conteduca, an Associate Professor at the University of Foggia in Italy. She will be discussing with us her recent presentation at the ESMO 2024 meeting on sequencing of radium followed by docetaxel or docetaxel followed by radium in patients with metastatic castration-resistant prostate cancer. Dr. Conteduca, thank you very much for joining us today. Would you be able to please tell us about your research and presentation at the ESMO meeting?
Vincenza Conteduca: Thank you very much for your introduction. I'm very happy to be here today and to share my preliminary data from the RAPSON trial that I presented at the ESMO 2024, so just one week ago.
This is an open-label, multicenter randomized trial of treatment sequencing between radium-223 and docetaxel in mCRPC patients. One of the most important questions for developing my trial is: For patients progressing on androgen receptor pathway inhibitors, is docetaxel or radium-223 the preferred choice? This is a very important question, particularly after some trials presented before during the ESMO conference—for example, PEACE-3 in evaluating the combination between enzalutamide plus radium-223 in patients that didn't get before androgen receptor pathway inhibitors.
Based on this key question, in 2015, I developed this RAPSON study including patients affected with symptomatic bone-dominant mCRPC progressing after any ADT, abiraterone, and/or enzalutamide. These patients were randomized 1:1 into two arms. In the first arm, patients received radium-223 and then, at progression, docetaxel. In the second arm, patients received docetaxel and then, at progression, radium-223. The step two is optional according to the clinical evolution of disease, including the onset of visceral metastasis or poor clinical conditions.
The primary endpoint of the RAPSON trial is a change in quality of life. Secondary endpoints are progression-free survival, total progression-free survival, overall survival, safety, and the identification of biomarkers. In patients receiving radium-223, the assessment of a patient's bone status is mandatory, and particularly they usually receive bone-targeting drugs to avoid fractures. The sample size of this study is 70 patients. We had no stratification factors.
For the assessment of quality of life in this trial, we use two different scores: FACT-P score and Bone Pain Inventory for bone pain intensity. We perform these two scores at different time points of the trial—so at baseline, during treatment, and at progression. One of the most important time points is 12 weeks, representing one of the most important timings for evaluating the change of quality of life in our patients.
Let's start with some preliminary clinical data from this trial, particularly quality of life. We can see a change in FACT-P quality of life score from baseline to week 12. In particular, we observe a deterioration in quality of life from baseline to week 12 in patients receiving docetaxel compared to patients receiving radium-223. Then we perform quality of life analysis within each treatment arm. So we can see a significant worsening in quality of life within only the docetaxel arm between baseline and 12-week evaluation. We can see this significant difference in quality of life from baseline and 12 weeks in patients receiving radium-223.
In addition, we perform a responder analysis only for bone pain intensity. A responder analysis showed a higher incidence of responders in terms of pain intensity and its interference with daily activity in radium-223 patients versus docetaxel-treated patients. In addition, we look at the quality of life in terms of tolerability, and so we checked for the treatment discontinuation rates in the docetaxel arm and within the radium-223 arm. We found a higher treatment discontinuation rate in patients receiving docetaxel compared to patients receiving radium-223. In fact, we observed seven treatment discontinuations in the docetaxel arm versus two treatment discontinuations in the radium-223 arm.
In addition, we perform a survival analysis, but I would like to better specify that the survival analysis is just a secondary endpoint of this trial, and in particular we look at the progression-free survival and overall survival. So far, they are just preliminary data, but in my opinion, they are a bit interesting.
In patients receiving radium-223, we observed a progression-free survival of 7.3 months compared to patients receiving docetaxel with a PFS of 9.7 months. We didn't obtain a significant difference between these two arms. In addition, we look at the overall survival. It was not reached in patients receiving radium-223, and it was 17.4 months in patients receiving docetaxel with a p-value of 0.964. So we didn't observe any significant difference between these two arms.
Based on this preliminary data, we can say in conclusion that the RAPSON trial provided preliminary evidence to support the use of radium-223 prior to chemotherapy in bone-dominant symptomatic mCRPC patients with clinical benefits in terms of better quality of life and tolerability. We observe no treatment differences in PFS and OS between the two treatment sequence arms, but additional follow-up and ongoing identification of outcome predictors might allow a more personalized approach to this sequential therapy strategy in mCRPC patients.
Neeraj Agarwal: Thank you very much. That was wonderful, and congratulations again for doing this very pertinent study looking at the sequencing of radium-223 followed by docetaxel or docetaxel followed by radium-223. So, Dr. Conteduca, if I want to summarize this for our audience, it looks like you took patients who had bone-predominant metastasis, they had symptomatic mCRPC, and when you treat them with radium followed by docetaxel or docetaxel followed by radium, it seems like the secondary outcomes of survivals, PFS or OS, they remain similar in both arms. But patients seem to have maintained a better quality of life as far as radium followed by docetaxel was concerned. Is that correct?
Vincenza Conteduca: Yes.
Neeraj Agarwal: Okay.
Vincenza Conteduca: That is a good question. This is a nice topic because it is, in my opinion, very interesting, especially so far because we have several available drugs for mCRPC patients, but we use a lot of these drugs in every stage of disease, like metastatic—for example, metastatic hormone-sensitive prostate cancer. So when we arrive in the mCRPC setting, we need to know exactly what is the best strategy for our patients. Probably I think quality of life as a primary endpoint is one of the most important aspects that we have to consider in our patients because we prolong a lot the survival in these patients thanks to new drugs. But we need to know what is the exactly better tolerated treatment sequence in our patients. I think the quality of life as a primary endpoint is challenging, but I think is innovative, especially is very helpful for our patients.
You're right, I show preliminary data on survival, PFS, OS. They are interesting, but I would like to underline that they are just secondary endpoints because they are preliminary data. We have a few patients with ongoing treatments, so we need to have the update of this data, probably next ESMO. I don't know for the next ESMO Conference, but they look great because if we don't have differences in terms of survival, I think the primary endpoint is quality of life is our best choice for our patients.
Neeraj Agarwal: That's wonderful. Thank you so much. So it looks like in the context of the PEACE-3 presentation, which was presented by Dr. Gillessen and team at the ESMO meeting, we have a choice of using radium plus enzalutamide. The survival outcomes were quite striking, both PFS and OS, and now we have these data which support good quality of life or at least quality of life seems to be better with radium followed by docetaxel chemotherapy. How do you see yourself sequencing in your clinic moving forward, assuming both drugs are available?
Vincenza Conteduca: Yeah, this is a good question, and I think all these studies that you mentioned are the background of my study because my study is just a Phase 2 trial.
Neeraj Agarwal: Yeah.
Vincenza Conteduca: So you mentioned ALSYMPCA and the PEACE-3 study that have Phase 3. I think my study, it's a small role, but it's very important because it included just a subset of patients progressing on ADT, enzalutamide, and abiraterone. So it's a different setting from PEACE-3 and in particular from the ALSYMPCA trial. The RAPSON trial has a different endpoint because it aims to assess the best treatment sequencing, so not just the role of radium-223. We have some patients progressing after docetaxel, but also prior to chemotherapy disease. It's very challenging to give radium-223 before docetaxel even also after androgen receptor pathway inhibitors. So I think probably the RAPSON trial could represent an aspect in the overall management of mCRPC patients.
Neeraj Agarwal: Thank you very much. So that concludes our discussion. I'd like to thank again on behalf of our viewers, Dr. Vincenza Conteduca, for taking the time to join us today. Thank you.
Vincenza Conteduca: Thank you for this opportunity to share this data, and I'm happy to update my data very soon. Thank you very much.