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*For medical professionals to read for reference only, Professor Dai Bo will take you to understand the latest progress of metastatic hormone-sensitive prostate cancer! The incidence of prostate cancer in Chinese patients is different from that in Western European and American countries.
50% of prostate cancer patients in China are metastatic hormone-sensitive type (mHSPC) at the time of diagnosis
.
Recently, the top journal NEJM published a new study of prostate cancer, which explored the survival benefit of dalotamide + androgen deprivation therapy + docetaxel
.
What is the effect of triple therapy? Is it expected to change clinical practice? "Medical Cancer Channel" specially invited Professor Dai Bo from Fudan University Affiliated Cancer Hospital to give readers a heartfelt interpretation
.
To answer a major "historical problem", the ARASENS study confirmed the benefit of triple therapy for OS Q medical community: Could you please introduce the findings of this study? ▎Professor Dai Bo said: "In the past three to four years, mHSPC-related research has made considerable progress, and a variety of new androgen signaling pathway inhibitors have been applied in the treatment of mHSPC
.
Studies have shown that abiraterone, Apalutamide, enzalutamide combined with ADT therapy can prolong the overall survival (OS) of patients compared with ADT alone
.
Subsequent CHAARTED study further showed that the addition of docetaxel to traditional ADT can also prolong the survival time.
In contrast to the ARASENS study, the investigators did not compare dalotamide plus ADT with ADT monotherapy to demonstrate an "expected" OS benefit .
Instead , the investigators The mHSPC patients were randomly divided into two groups.
The treatment group received ADT + darotamide + 6 cycles of docetaxel (triple therapy); the control group received standard treatment, namely ADT + placebo + 6 cycles of docetaxel treatment .
The results showed that triple therapy of ADT + dalotamide + docetaxel could further prolong the OS of patients (HR 0.
68; 95% CI 0.
57-0.
80; P<0.
001).
Key secondary endpoints such as time to cancer (CRPC) and time to pain progression also improved
.
This means the birth of a whole new treatment regimen
.
The ARASENS study takes mHSPC-related research and overall treatment strategies a step further
.
"The results of the ARASENS study have actually been explored by researchers before triple therapy.
The PEACE-1 study reported at the 2021 ESMO Annual Meeting is a phase III trial using a 2x2 factorial design, aiming to explore the role of standard of care (SOC) Based on this, whether combined with abiraterone or radiotherapy can further improve the survival of mHSPC patients
.
However, since the PEACE-1 study started in 2013, the SOC of mHSPC patients was changed from ADT monotherapy to ADT + docetaxel during the study period, so 1173 cases were Among the mHSPC patients, 710 patients had SOC of ADT + docetaxel
.
The results showed that in the SOC of ADT + docetaxel, the combination of abiraterone significantly improved OS (NR vs 4.
4 years; HR 0.
75, 95% CI 0.
59-0.
96; P=0.
021)
.
The PEACE-1 study design Unfortunately, although the PEACE-1 study also found that the triple therapy of novel androgen signaling pathway inhibitors + ADT + docetaxel can improve the patient's OS, receiving triple therapy of patients were only a subgroup in the PEACE-1 study, and not all patients in this subgroup included docetaxel in their treatment regimens, so the PEACE-1 study was not as high-level of evidence-based medicine as the ARASENS study
.
It can be said that it is designed to answer this "historical problem"
.
Carrying some "Chinese ancestry", the ARASENS study may soon change clinical practice Q medical community: What do you think is novel about this study? What are the implications of the results of this study for clinical practice in my country? ▎Professor Dai Bo: "Because the ARASENS study is a large-scale Phase III study with thousands of patients, and the P value is statistically significant (P<0.
001) while achieving positive results, it is almost impossible to There may be false positives
.
Therefore, there is no doubt that the ARASENS study will bring changes to clinical practice, and relevant domestic and foreign guidelines will add this content in the next update
.
However, it is worth noting that in clinical practice, due to different Patients' physical conditions are different, and not all patients can tolerate such triple therapy
.
Among the patients enrolled in the ARASENS study, patients with an ECOG score of 0 and 1 accounted for about 70% and 30%, respectively.
The vast majority of the patients in this study are in good physical condition, so they can tolerate such triple therapy
.
However, some patients with poor physical condition and weak heart, liver and kidney function may not be able to tolerate it
.
In this study, the triple therapy group appeared The proportion of patients with adverse reactions of grade 3 and above exceeds 70%, but the vast majority of adverse reactions of grade 3 or above are neutropenia
.
Although on the basis of the preventive application of white medicine, patients are likely to be able to successfully complete the treatment plan, However, in practice, clinicians still need to screen suitable patients under the premise of considering the individual conditions of patients, and cannot "generalize" all patients
.
The ARASENS study has the following advantages
.
First, the patients enrolled in the ARASENS study include Asian patients , and patients in the Asia-Pacific region account for about 30%.
Researchers from all over China, represented by Professor Ye Dingwei from our hospital, also participated in the ARASENS study.
.
Therefore, when this treatment plan is applied to domestic prostate cancer patients, it may not be necessary to consider the problem of "acclimatization", and domestic patients can benefit from it
.
Second, the patients enrolled in the ARASENS study can reflect the real clinical situation
.
The study enrolled both patients with newly diagnosed oligometastases (85.
7%) and patients with disease recurrence and metastasis (13.
2%) after radical treatment
.
The clinical characteristics of the patients enrolled in the study were typical, with higher Gleason scores (≥8 points) and higher prostate cancer-specific antigen (PSA) levels, which better reflected the real situation of patients in clinical practice
.
The study demonstrated that patients with recurrence and metastasis can also benefit from triple therapy
.
"Opening new ideas, ARASENS research reveals new directions for exploration.
Q: What do you think can be optimized in this research? What questions does this research raise? ▎Professor Dai Bo said: "In fact, any one Research cannot solve all problems
.
This study mainly answered the question of whether the addition of dalotamide to ADT + docetaxel can further prolong the OS of patients.
The unanswered questions include: the investigators choose to use 6 cycles of docetaxel treatment , whose evidence-based medical evidence actually comes from the CHAARTED study
.
However, in the real world, not all patients can withstand 6 cycles of chemotherapy, or do not need to use 6 cycles to get a good effect, or the disease has not reached the maximum remission after 6 cycles of treatment
.
Therefore, whether 6 cycles of docetaxel treatment must be the best solution in the triple therapy of "Dalotamide + ADT + Docetaxel" deserves further exploration
.
This study "opened up new ideas" for follow-up clinical research - dalotamide is a novel androgen signaling pathway inhibitor, and its mechanism of action is similar to abiraterone, enzalutamide, apalutamide, etc.
, then Could other novel androgen signaling pathway inhibitors be able to replicate the same studies and reach the same conclusions? This is also worth exploring
.
"I think there is a high possibility that such a study can be repeated in theory, but it still needs to be viewed dialectically before the evidence-based medical evidence for other novel androgen signaling pathway inhibitors is implemented
.
other novel androgen signaling pathway inhibitors can be considered instead, as a 'workaround', but the use of dalotamide is currently the program with the highest level of evidence-based medical evidence
.
" The professor concluded
.
Expert Profile Professor Dai Bo, MD, Chief Physician, Doctoral Supervisor, Director of Urology Department, Fudan University Affiliated Tumor Hospital Standing Committee Member of Shanghai Association of Urology Act as editorial board member of the following academic journals: "Chinese Journal of Urology", "Chinese Journal of Cancer", "Journal of Southern Medical University", "Chinese Journal of Cancer Prevention and Treatment" "Chief Minimally Invasive Surgery Chief Surgeon" of the Department of Oncology Special Committee for two sessions of "MDT Outstanding Physician" of the Chinese Anti-Cancer Association Urology and Male Genital Oncology Special Committee Oncology field) Two-time "Good Doctor of the Year" Shanghai Urological Society Annual Man of the Year, Benevolent Physician (Nomination Award for Shanghai Outstanding Specialist Award) Outstanding Young Talents of Shanghai Health System, Fudan University Top Ten Medical Youth Reference Source: [1].
Smith MR, Hussain M, Saad F, et al.
Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer.
N Engl J Med.
2022 Feb 17.
doi: 10.
1056/NEJMoa2119115.
50% of prostate cancer patients in China are metastatic hormone-sensitive type (mHSPC) at the time of diagnosis
.
Recently, the top journal NEJM published a new study of prostate cancer, which explored the survival benefit of dalotamide + androgen deprivation therapy + docetaxel
.
What is the effect of triple therapy? Is it expected to change clinical practice? "Medical Cancer Channel" specially invited Professor Dai Bo from Fudan University Affiliated Cancer Hospital to give readers a heartfelt interpretation
.
To answer a major "historical problem", the ARASENS study confirmed the benefit of triple therapy for OS Q medical community: Could you please introduce the findings of this study? ▎Professor Dai Bo said: "In the past three to four years, mHSPC-related research has made considerable progress, and a variety of new androgen signaling pathway inhibitors have been applied in the treatment of mHSPC
.
Studies have shown that abiraterone, Apalutamide, enzalutamide combined with ADT therapy can prolong the overall survival (OS) of patients compared with ADT alone
.
Subsequent CHAARTED study further showed that the addition of docetaxel to traditional ADT can also prolong the survival time.
In contrast to the ARASENS study, the investigators did not compare dalotamide plus ADT with ADT monotherapy to demonstrate an "expected" OS benefit .
Instead , the investigators The mHSPC patients were randomly divided into two groups.
The treatment group received ADT + darotamide + 6 cycles of docetaxel (triple therapy); the control group received standard treatment, namely ADT + placebo + 6 cycles of docetaxel treatment .
The results showed that triple therapy of ADT + dalotamide + docetaxel could further prolong the OS of patients (HR 0.
68; 95% CI 0.
57-0.
80; P<0.
001).
Key secondary endpoints such as time to cancer (CRPC) and time to pain progression also improved
.
This means the birth of a whole new treatment regimen
.
The ARASENS study takes mHSPC-related research and overall treatment strategies a step further
.
"The results of the ARASENS study have actually been explored by researchers before triple therapy.
The PEACE-1 study reported at the 2021 ESMO Annual Meeting is a phase III trial using a 2x2 factorial design, aiming to explore the role of standard of care (SOC) Based on this, whether combined with abiraterone or radiotherapy can further improve the survival of mHSPC patients
.
However, since the PEACE-1 study started in 2013, the SOC of mHSPC patients was changed from ADT monotherapy to ADT + docetaxel during the study period, so 1173 cases were Among the mHSPC patients, 710 patients had SOC of ADT + docetaxel
.
The results showed that in the SOC of ADT + docetaxel, the combination of abiraterone significantly improved OS (NR vs 4.
4 years; HR 0.
75, 95% CI 0.
59-0.
96; P=0.
021)
.
The PEACE-1 study design Unfortunately, although the PEACE-1 study also found that the triple therapy of novel androgen signaling pathway inhibitors + ADT + docetaxel can improve the patient's OS, receiving triple therapy of patients were only a subgroup in the PEACE-1 study, and not all patients in this subgroup included docetaxel in their treatment regimens, so the PEACE-1 study was not as high-level of evidence-based medicine as the ARASENS study
.
It can be said that it is designed to answer this "historical problem"
.
Carrying some "Chinese ancestry", the ARASENS study may soon change clinical practice Q medical community: What do you think is novel about this study? What are the implications of the results of this study for clinical practice in my country? ▎Professor Dai Bo: "Because the ARASENS study is a large-scale Phase III study with thousands of patients, and the P value is statistically significant (P<0.
001) while achieving positive results, it is almost impossible to There may be false positives
.
Therefore, there is no doubt that the ARASENS study will bring changes to clinical practice, and relevant domestic and foreign guidelines will add this content in the next update
.
However, it is worth noting that in clinical practice, due to different Patients' physical conditions are different, and not all patients can tolerate such triple therapy
.
Among the patients enrolled in the ARASENS study, patients with an ECOG score of 0 and 1 accounted for about 70% and 30%, respectively.
The vast majority of the patients in this study are in good physical condition, so they can tolerate such triple therapy
.
However, some patients with poor physical condition and weak heart, liver and kidney function may not be able to tolerate it
.
In this study, the triple therapy group appeared The proportion of patients with adverse reactions of grade 3 and above exceeds 70%, but the vast majority of adverse reactions of grade 3 or above are neutropenia
.
Although on the basis of the preventive application of white medicine, patients are likely to be able to successfully complete the treatment plan, However, in practice, clinicians still need to screen suitable patients under the premise of considering the individual conditions of patients, and cannot "generalize" all patients
.
The ARASENS study has the following advantages
.
First, the patients enrolled in the ARASENS study include Asian patients , and patients in the Asia-Pacific region account for about 30%.
Researchers from all over China, represented by Professor Ye Dingwei from our hospital, also participated in the ARASENS study.
.
Therefore, when this treatment plan is applied to domestic prostate cancer patients, it may not be necessary to consider the problem of "acclimatization", and domestic patients can benefit from it
.
Second, the patients enrolled in the ARASENS study can reflect the real clinical situation
.
The study enrolled both patients with newly diagnosed oligometastases (85.
7%) and patients with disease recurrence and metastasis (13.
2%) after radical treatment
.
The clinical characteristics of the patients enrolled in the study were typical, with higher Gleason scores (≥8 points) and higher prostate cancer-specific antigen (PSA) levels, which better reflected the real situation of patients in clinical practice
.
The study demonstrated that patients with recurrence and metastasis can also benefit from triple therapy
.
"Opening new ideas, ARASENS research reveals new directions for exploration.
Q: What do you think can be optimized in this research? What questions does this research raise? ▎Professor Dai Bo said: "In fact, any one Research cannot solve all problems
.
This study mainly answered the question of whether the addition of dalotamide to ADT + docetaxel can further prolong the OS of patients.
The unanswered questions include: the investigators choose to use 6 cycles of docetaxel treatment , whose evidence-based medical evidence actually comes from the CHAARTED study
.
However, in the real world, not all patients can withstand 6 cycles of chemotherapy, or do not need to use 6 cycles to get a good effect, or the disease has not reached the maximum remission after 6 cycles of treatment
.
Therefore, whether 6 cycles of docetaxel treatment must be the best solution in the triple therapy of "Dalotamide + ADT + Docetaxel" deserves further exploration
.
This study "opened up new ideas" for follow-up clinical research - dalotamide is a novel androgen signaling pathway inhibitor, and its mechanism of action is similar to abiraterone, enzalutamide, apalutamide, etc.
, then Could other novel androgen signaling pathway inhibitors be able to replicate the same studies and reach the same conclusions? This is also worth exploring
.
"I think there is a high possibility that such a study can be repeated in theory, but it still needs to be viewed dialectically before the evidence-based medical evidence for other novel androgen signaling pathway inhibitors is implemented
.
other novel androgen signaling pathway inhibitors can be considered instead, as a 'workaround', but the use of dalotamide is currently the program with the highest level of evidence-based medical evidence
.
" The professor concluded
.
Expert Profile Professor Dai Bo, MD, Chief Physician, Doctoral Supervisor, Director of Urology Department, Fudan University Affiliated Tumor Hospital Standing Committee Member of Shanghai Association of Urology Act as editorial board member of the following academic journals: "Chinese Journal of Urology", "Chinese Journal of Cancer", "Journal of Southern Medical University", "Chinese Journal of Cancer Prevention and Treatment" "Chief Minimally Invasive Surgery Chief Surgeon" of the Department of Oncology Special Committee for two sessions of "MDT Outstanding Physician" of the Chinese Anti-Cancer Association Urology and Male Genital Oncology Special Committee Oncology field) Two-time "Good Doctor of the Year" Shanghai Urological Society Annual Man of the Year, Benevolent Physician (Nomination Award for Shanghai Outstanding Specialist Award) Outstanding Young Talents of Shanghai Health System, Fudan University Top Ten Medical Youth Reference Source: [1].
Smith MR, Hussain M, Saad F, et al.
Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer.
N Engl J Med.
2022 Feb 17.
doi: 10.
1056/NEJMoa2119115.
