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*Only for medical professionals to read for reference.
On February 11-13, 2021, the American Society of Clinical Oncology Symposium on Urogenital System Oncology (ASCO-GU) was successfully held online.
The conference announced a number of major urinary oncology fields.
Research result.
This article will share the heavy oral report data in the field of prostate cancer: the correlation between molecular characteristics and long-term efficacy in the follow-up analysis of the SPARTAN study, and invited Professor Liao Hong from Sichuan Cancer Hospital to conduct an in-depth interpretation.
Abstract 8: The correlation between the molecular characteristics of apatamide in the treatment of NM-CRPC and the long-term efficacy [1] SPARTAN study [2] is a global multi-center, randomized, double-blind, placebo-controlled phase III clinical trial, evaluation The effectiveness and safety of apatamide + androgen deprivation therapy (ADT) in the treatment of non-metastatic castration-resistant prostate cancer (NM-CRPC).
A total of 1207 NM-CRPC patients with high risk of metastasis were enrolled in the study, and they were randomly assigned to the apatamide+ADT group and placebo+ADT group according to a 2:1 ratio.
The primary endpoint of the study is metastasis-free survival (MFS), and secondary endpoints include progression-free survival (PFS), time to symptom progression, overall survival (OS), and time to cytotoxic chemotherapy.
In this follow-up analysis, molecular markers related to the long-term efficacy of apatamide were explored.
According to the time of metastasis, the subjects in the SPARTAN study were divided into two groups: long-term response group (LTR, long- term responder) and early progressor (EP, early progressor).
The study compared the expression of genes related to cancer biology in the LTR group and the EP group to explore the correlation between molecular characteristics and long-term efficacy.
The results showed that in the LTR group, the median MFS of patients treated with apatamide and placebo were 40.
5 months and 22 months, respectively; in the EP group, the median MFS of patients treated with apatamide and placebo was 40.
5 months.
The MFS is 7.
3 months and 3.
6 months respectively.
From the results of molecular characteristics, the gene expression characteristics related to the long-term response of apatamide include: T cell activation, T cell stimulation, cytokine response, interferon production, reduced T cell rejection, low proliferation capacity, and high hormone dependence .
The molecular typing characteristics closely related to early progress include high-risk (Decipher detection high-risk and high risk of metastasis), hormonal non-response (Basal type and low AR activity), and neuroendocrine characteristics.
(Table 1).
Table 1 Molecular characteristics related to the long-term response and early progression of apatamide.
In addition, unlike the placebo group, in patients treated with apatamide, strong T cell proliferation at baseline can further prolong the patient's MFS , Delaying the occurrence of metastasis, which suggests that our T cell proliferation capacity is related to whether there is a better response to apatamide treatment (Figure 1).
Figure 1 The relationship between T cell proliferation and MFS in patients.
PAM50 classification has gradually become a hot spot in the field of prostate cancer in recent years.
Previous studies have shown that Luminal-type patients are sensitive to ADT treatment, while Basal-type patients have an unsatisfactory response to ADT treatment [3].
The report on the molecular typing of the SPARTAN study at the ASCO conference in 2020 has shown that [4] that apatamide combined with ADT treatment can prolong the survival time of Basal patients and benefit patients compared with ADT alone (Figure 2) .
The results of further analysis in this meeting showed that if Basal-type patients have strong T cell proliferation, the use of apatamide combined with ADT can further delay the time of metastasis in patients, which is similar to the benefits of Luminal-type patients.
This reminds us that NM-CRPC patients with strong T cell proliferation can benefit from apatamide combined with ADT treatment to a greater extent.
Figure 2 T cell proliferation ability to benefit analysis of apatamide treatment of Basal patients Expert comment (Professor Liao Hong from Sichuan Cancer Hospital) NM-CRPC is an objective and independent clinical disease state.
This concept is derived from prostate cancer The Collaboration Group (PCWG) proposed for the first time in the third standard update working meeting in 2016 [5].
The diagnosis needs to meet: "castration resistance" and "traditional imaging without metastasis" two key points, but in fact, in clinical work, many experts report that patients rarely encounter NM-CRPC, my country's PC-follow database Statistics also show that my country's NM-CRPC patients account for only 14.
3% of all CRPC patients[6], which is lower than that of European and American countries.
In fact, there are two reasons for the low diagnosis rate of NM-CRPC.
One is that most patients in my country only seek medical attention when they are symptomatic, and most of the patients have metastasis at the time of medical treatment; in addition, for the limited and late use of continuous endocrine therapy For patients, our follow-up was not timely enough, so that the prostate-specific antigen (PSA) has risen to a high level, and CRPC is not diagnosed until metastasis has occurred, which missed the timing of the diagnosis of NM-CRPC.
This reminds us that regular PSA follow-up and imaging monitoring should be carried out in the clinic to identify early CRPC patients and provide them with a more effective treatment plan as soon as possible.
At present, the main treatment for NM-CRPC patients in my country is still traditional endocrine therapy, and whether it is ADT or combined androgen blockade (CAB), the efficacy of high-risk NM-CRPC is very limited, and it cannot effectively delay distant metastases.
occur.
The emergence of apatamide has brought a fundamental change in the treatment of high-risk NM-CRPC patients.
The SPARTAN study has shown that apatamide can maintain MFS for up to 40.
5 months [7].
According to the final OS data released at the ASCO conference in 2020, the median OS of patients in the apatamide group was 73.
9 months, which was significantly longer than that in the placebo group by 14 months.
If the patients who were transferred to the group after the study was unblinded were excluded As a result, the OS benefit of the apatamide group reached 21.
2 months [8].
This super long-term benefit result can be said to give a perfect answer to the efficacy of apatamide in the treatment of NM-CRPC patients.
When prostate cancer develops to an advanced stage, how to accurately judge the aggressiveness of the tumor at the individual level is crucial for doctors to make better treatment decisions and formulate treatment plans.
In the past few years, new treatments for NM-CRPC have also increased, and how to better choose treatment options has also become a puzzle for clinicians.
In response to this problem, some molecular classifications based on the clinical and pathological characteristics of prostate cancer have been extensively studied and applied to various disease stages.
In the NM-CRPC stage, Decipher GC score and PAM50 classification also have certain applications.
The results of the study show that apatamide can improve the poor prognosis of patients with high-risk GC, and make the benefits of high-risk GC and Luminal subtype OS more significant.
[4].
In further analysis of molecular characteristics, it was also found that NM-CRPC patients with strong T cell proliferation ability can benefit from the treatment of apatamide combined with ADT to a greater extent.
Although these detection methods are not yet popular in clinical practical applications at this stage, they also provide a direction and preliminary basis for our future research and selection of treatment strategies.
We also look forward to the emergence of more relevant markers and corresponding treatment options.
Realize precise treatment under the guidance of biomarkers at the molecular level of prostate cancer.
We have witnessed the leap from no effective drugs in the treatment of NM-CRPC to a new era of blooming flowers.
We believe that with the continuous in-depth research of new treatment options, prostate cancer patients can achieve longer and more quality survival.
The diagnosis and treatment of prostate cancer are also constantly being explored and developed.
The clinical application value of new imaging tests such as PSMA PET-CT, genetic testing, and precision treatment are all issues that are worth exploring.
I believe that with the continuous deepening of research, There will be more achievements and progress in the field of prostate cancer in the future. Expert profile Professor Liao Hong Chief physician, researcher, and master's tutor.
Director of Urology Department of Sichuan Cancer Hospital.
Leader of Academic Technology of Sichuan Health Committee.
Member of Chinese Anticancer Association Urinary and Male Reproductive Tumor Committee Member of Chinese Society of Clinical Oncology (CSCO) Prostate Member of the Cancer Expert Committee Member of the Prostate Cancer Group of the Chinese Anti-Cancer Association Urinary and Male Reproductive Tumor Committee Member of the Endoscopic and Minimally Invasive Technology Branch of the Chinese Medical Equipment Association Deputy Chairman of the Urinary and Male Reproductive Tumor Committee of the Sichuan Anti-Cancer Association Sichuan Member of the Urology Committee of the Provincial Geriatrics Association Vice Chairman of the Urology Committee of the Sichuan Rehabilitation Medicine Association Member of the Standing Committee of the Accelerated Rehabilitation Surgery Branch of the Sichuan Rehabilitation Medicine Association Member of the Urology Committee of the Sichuan Medical Association Urology Oncology of the Sichuan Medical Association The deputy leader of the group, the member of the Urology Branch of the Sichuan Medical Association, the member of the Outpatient Management Committee of the Sichuan Medical Association, the member of the Urology Branch of the Chengdu Medical Association, the deputy leader of the Advanced Renal Cancer Group "JCO-Urinary and Male Genital Tumor Special Issue" Editorial Board "Tumor Prevention and Treatment" References: 1.
Felix Y.
Feng et al.
Molecular determinants associated with long-term response to apalutamide (APA) in nonmetastatic castration-resistant prostate cancer (nmCRPC).
ASCO- GU 2021 Abstract 8.
2.
Smith, MR, et al.
, Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.
N Engl J Med, 2018.
378(15): p.
1408-1418.
3.
Zhao SG, Chang SL, Erho N , et al.
JAMA Oncol.
2017;3(12):1663–1672.
doi:10.
1001/jamaoncol.
2017.
07514.
Fred Saad,et al.
Molecular determinants ofprostate specific antigen (PSA)kinetics and clinical response to apalutamide (APA) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in SPARTAN.
2020 ASCO.
Abstract 5521.
5.
Scher HI, Morris MJ, Stadler WM, et al.
Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3.
J Clin Oncol.
2016 Apr 20;34(12):1402-18.
6.
Xu Gao, ea, PC based -Follow database: A real-world study of prostate cancer: Current status of diagnosis and treatment of CRPC patients in China 2019 CUA.
2019.
7.
Smith, MR, et al.
, Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.
N Engl J Med, 2018.
378(15) : p.
1408-1418.
8.
Eric Jay Small, FS, Simon Chowdhury, Final survival results from SPARTAN,a phase III study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC).
ASCO 2020, 2020.
Abstract 5516.
On February 11-13, 2021, the American Society of Clinical Oncology Symposium on Urogenital System Oncology (ASCO-GU) was successfully held online.
The conference announced a number of major urinary oncology fields.
Research result.
This article will share the heavy oral report data in the field of prostate cancer: the correlation between molecular characteristics and long-term efficacy in the follow-up analysis of the SPARTAN study, and invited Professor Liao Hong from Sichuan Cancer Hospital to conduct an in-depth interpretation.
Abstract 8: The correlation between the molecular characteristics of apatamide in the treatment of NM-CRPC and the long-term efficacy [1] SPARTAN study [2] is a global multi-center, randomized, double-blind, placebo-controlled phase III clinical trial, evaluation The effectiveness and safety of apatamide + androgen deprivation therapy (ADT) in the treatment of non-metastatic castration-resistant prostate cancer (NM-CRPC).
A total of 1207 NM-CRPC patients with high risk of metastasis were enrolled in the study, and they were randomly assigned to the apatamide+ADT group and placebo+ADT group according to a 2:1 ratio.
The primary endpoint of the study is metastasis-free survival (MFS), and secondary endpoints include progression-free survival (PFS), time to symptom progression, overall survival (OS), and time to cytotoxic chemotherapy.
In this follow-up analysis, molecular markers related to the long-term efficacy of apatamide were explored.
According to the time of metastasis, the subjects in the SPARTAN study were divided into two groups: long-term response group (LTR, long- term responder) and early progressor (EP, early progressor).
The study compared the expression of genes related to cancer biology in the LTR group and the EP group to explore the correlation between molecular characteristics and long-term efficacy.
The results showed that in the LTR group, the median MFS of patients treated with apatamide and placebo were 40.
5 months and 22 months, respectively; in the EP group, the median MFS of patients treated with apatamide and placebo was 40.
5 months.
The MFS is 7.
3 months and 3.
6 months respectively.
From the results of molecular characteristics, the gene expression characteristics related to the long-term response of apatamide include: T cell activation, T cell stimulation, cytokine response, interferon production, reduced T cell rejection, low proliferation capacity, and high hormone dependence .
The molecular typing characteristics closely related to early progress include high-risk (Decipher detection high-risk and high risk of metastasis), hormonal non-response (Basal type and low AR activity), and neuroendocrine characteristics.
(Table 1).
Table 1 Molecular characteristics related to the long-term response and early progression of apatamide.
In addition, unlike the placebo group, in patients treated with apatamide, strong T cell proliferation at baseline can further prolong the patient's MFS , Delaying the occurrence of metastasis, which suggests that our T cell proliferation capacity is related to whether there is a better response to apatamide treatment (Figure 1).
Figure 1 The relationship between T cell proliferation and MFS in patients.
PAM50 classification has gradually become a hot spot in the field of prostate cancer in recent years.
Previous studies have shown that Luminal-type patients are sensitive to ADT treatment, while Basal-type patients have an unsatisfactory response to ADT treatment [3].
The report on the molecular typing of the SPARTAN study at the ASCO conference in 2020 has shown that [4] that apatamide combined with ADT treatment can prolong the survival time of Basal patients and benefit patients compared with ADT alone (Figure 2) .
The results of further analysis in this meeting showed that if Basal-type patients have strong T cell proliferation, the use of apatamide combined with ADT can further delay the time of metastasis in patients, which is similar to the benefits of Luminal-type patients.
This reminds us that NM-CRPC patients with strong T cell proliferation can benefit from apatamide combined with ADT treatment to a greater extent.
Figure 2 T cell proliferation ability to benefit analysis of apatamide treatment of Basal patients Expert comment (Professor Liao Hong from Sichuan Cancer Hospital) NM-CRPC is an objective and independent clinical disease state.
This concept is derived from prostate cancer The Collaboration Group (PCWG) proposed for the first time in the third standard update working meeting in 2016 [5].
The diagnosis needs to meet: "castration resistance" and "traditional imaging without metastasis" two key points, but in fact, in clinical work, many experts report that patients rarely encounter NM-CRPC, my country's PC-follow database Statistics also show that my country's NM-CRPC patients account for only 14.
3% of all CRPC patients[6], which is lower than that of European and American countries.
In fact, there are two reasons for the low diagnosis rate of NM-CRPC.
One is that most patients in my country only seek medical attention when they are symptomatic, and most of the patients have metastasis at the time of medical treatment; in addition, for the limited and late use of continuous endocrine therapy For patients, our follow-up was not timely enough, so that the prostate-specific antigen (PSA) has risen to a high level, and CRPC is not diagnosed until metastasis has occurred, which missed the timing of the diagnosis of NM-CRPC.
This reminds us that regular PSA follow-up and imaging monitoring should be carried out in the clinic to identify early CRPC patients and provide them with a more effective treatment plan as soon as possible.
At present, the main treatment for NM-CRPC patients in my country is still traditional endocrine therapy, and whether it is ADT or combined androgen blockade (CAB), the efficacy of high-risk NM-CRPC is very limited, and it cannot effectively delay distant metastases.
occur.
The emergence of apatamide has brought a fundamental change in the treatment of high-risk NM-CRPC patients.
The SPARTAN study has shown that apatamide can maintain MFS for up to 40.
5 months [7].
According to the final OS data released at the ASCO conference in 2020, the median OS of patients in the apatamide group was 73.
9 months, which was significantly longer than that in the placebo group by 14 months.
If the patients who were transferred to the group after the study was unblinded were excluded As a result, the OS benefit of the apatamide group reached 21.
2 months [8].
This super long-term benefit result can be said to give a perfect answer to the efficacy of apatamide in the treatment of NM-CRPC patients.
When prostate cancer develops to an advanced stage, how to accurately judge the aggressiveness of the tumor at the individual level is crucial for doctors to make better treatment decisions and formulate treatment plans.
In the past few years, new treatments for NM-CRPC have also increased, and how to better choose treatment options has also become a puzzle for clinicians.
In response to this problem, some molecular classifications based on the clinical and pathological characteristics of prostate cancer have been extensively studied and applied to various disease stages.
In the NM-CRPC stage, Decipher GC score and PAM50 classification also have certain applications.
The results of the study show that apatamide can improve the poor prognosis of patients with high-risk GC, and make the benefits of high-risk GC and Luminal subtype OS more significant.
[4].
In further analysis of molecular characteristics, it was also found that NM-CRPC patients with strong T cell proliferation ability can benefit from the treatment of apatamide combined with ADT to a greater extent.
Although these detection methods are not yet popular in clinical practical applications at this stage, they also provide a direction and preliminary basis for our future research and selection of treatment strategies.
We also look forward to the emergence of more relevant markers and corresponding treatment options.
Realize precise treatment under the guidance of biomarkers at the molecular level of prostate cancer.
We have witnessed the leap from no effective drugs in the treatment of NM-CRPC to a new era of blooming flowers.
We believe that with the continuous in-depth research of new treatment options, prostate cancer patients can achieve longer and more quality survival.
The diagnosis and treatment of prostate cancer are also constantly being explored and developed.
The clinical application value of new imaging tests such as PSMA PET-CT, genetic testing, and precision treatment are all issues that are worth exploring.
I believe that with the continuous deepening of research, There will be more achievements and progress in the field of prostate cancer in the future. Expert profile Professor Liao Hong Chief physician, researcher, and master's tutor.
Director of Urology Department of Sichuan Cancer Hospital.
Leader of Academic Technology of Sichuan Health Committee.
Member of Chinese Anticancer Association Urinary and Male Reproductive Tumor Committee Member of Chinese Society of Clinical Oncology (CSCO) Prostate Member of the Cancer Expert Committee Member of the Prostate Cancer Group of the Chinese Anti-Cancer Association Urinary and Male Reproductive Tumor Committee Member of the Endoscopic and Minimally Invasive Technology Branch of the Chinese Medical Equipment Association Deputy Chairman of the Urinary and Male Reproductive Tumor Committee of the Sichuan Anti-Cancer Association Sichuan Member of the Urology Committee of the Provincial Geriatrics Association Vice Chairman of the Urology Committee of the Sichuan Rehabilitation Medicine Association Member of the Standing Committee of the Accelerated Rehabilitation Surgery Branch of the Sichuan Rehabilitation Medicine Association Member of the Urology Committee of the Sichuan Medical Association Urology Oncology of the Sichuan Medical Association The deputy leader of the group, the member of the Urology Branch of the Sichuan Medical Association, the member of the Outpatient Management Committee of the Sichuan Medical Association, the member of the Urology Branch of the Chengdu Medical Association, the deputy leader of the Advanced Renal Cancer Group "JCO-Urinary and Male Genital Tumor Special Issue" Editorial Board "Tumor Prevention and Treatment" References: 1.
Felix Y.
Feng et al.
Molecular determinants associated with long-term response to apalutamide (APA) in nonmetastatic castration-resistant prostate cancer (nmCRPC).
ASCO- GU 2021 Abstract 8.
2.
Smith, MR, et al.
, Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.
N Engl J Med, 2018.
378(15): p.
1408-1418.
3.
Zhao SG, Chang SL, Erho N , et al.
JAMA Oncol.
2017;3(12):1663–1672.
doi:10.
1001/jamaoncol.
2017.
07514.
Fred Saad,et al.
Molecular determinants ofprostate specific antigen (PSA)kinetics and clinical response to apalutamide (APA) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in SPARTAN.
2020 ASCO.
Abstract 5521.
5.
Scher HI, Morris MJ, Stadler WM, et al.
Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3.
J Clin Oncol.
2016 Apr 20;34(12):1402-18.
6.
Xu Gao, ea, PC based -Follow database: A real-world study of prostate cancer: Current status of diagnosis and treatment of CRPC patients in China 2019 CUA.
2019.
7.
Smith, MR, et al.
, Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer.
N Engl J Med, 2018.
378(15) : p.
1408-1418.
8.
Eric Jay Small, FS, Simon Chowdhury, Final survival results from SPARTAN,a phase III study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC).
ASCO 2020, 2020.
Abstract 5516.
