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Prostate cancer is one of the most common male malignancies.
As the disease progresses, most of them will turn into castration-resistant prostate cancer (CRPC).
Therefore, the treatment of CRPC is a hot topic for urological oncologists.
On January 9, 2021, the 2021 New World Forum on Genitourinary Tumor and Enzalutamide Non-metastatic Castration-Resistant Prostate Cancer (nmCRPC) China Listing Conference was successfully held in Zhuhai.
In this meeting, Professor Han Bangmin from Shanghai First People's Hospital discussed how to measure the comprehensive benefits of first-line treatment for CRPC patients.
Pay attention to the first-line options of mCRPC treatment options ranging from localized/locally advanced prostate cancer, to metastatic hormone-sensitive prostate cancer (mHSPC), and then to CRPC.
There are different systemic treatment strategies for each stage of advanced prostate cancer.
Professor Han said that considering that less than 50% of mCRPC patients can receive second-line treatment, the mCRPC treatment plan should be placed on the first line.
The Chinese Society of Clinical Oncology (CSCO) Guidelines for Diagnosis and Treatment of Prostate Cancer (2020) recommend that the first-line treatment options for mCRPC include enzalutamide, abiraterone, docetaxel and radium-223.
The TAX-327 study confirmed for the first time that docetaxel has a survival benefit in the treatment of mCRPC patients, and the use of new endocrine therapy to replace docetaxel as a first-line treatment is gradually increasing.
A retrospective study analyzed data from the Veterans Health Administration (VA) database and included 3637 patients diagnosed with mCRPC from January 2006 to August 2015, and evaluated Epoch1 (from 2006 to 2010, 83% of patients were first-line The treatment was docetaxel chemotherapy) and Epoch2 (from 2011 to 2016, 62% of patients were treated with enzalutamide or abiraterone as first-line treatment) time to biochemical progression and OS.
The results showed that compared with Epoch1, Epoch2's time to biochemical progression (13 vs 9 months) and OS (23 vs 15 months) were both prolonged.
Figure 1.
Results of Epoch1 and Epoch2 The PREVALIL study and the COU-AA-302 study respectively confirmed that enzalutamide and abiraterone have OS benefits for mCRPC patients.
The PREVAIL study showed that enzalutamide significantly prolonged OS by 4 months compared with placebo group (35.
3 vs 31.
3 months); COU-AA-302 study showed that abiraterone combined with prednisone prolonged OS by 4.
4 months compared with placebo group (34.
7 vs 30.
3 months).
It is worth noting that, in the absence of head-to-head data, in real-world studies in Europe and America, enzalutamide has additional OS benefits compared to abiraterone: an American real-world study retrospectively analyzed data from the VA database , To compare the OS benefit of mCRPC patients receiving first-line enzalutamide or abiraterone, compared to the sequential regimen of bicalutamide after treatment for >90 days.
The results showed that compared with the first-line abiraterone cohort, patients receiving enzalutamide had an 11% lower risk of death and better OS.
Figure 2 Results of a real-world study in the United States A French real-world study used the French National Health Data System to directly compare the OS of mCRPC patients who had not received chemotherapy before using enzalutamide or abiraterone.
The results show that, compared with abiraterone, enzalutamide has a 10% OS advantage.
Figure 3 French real-world study results weighing appropriate patients with mCRPC first-line program Professor Han proposed that the choice of first-line treatment for mCRPC patients requires consideration of basic comorbidities, metastatic load/site, Gleason score, etc.
, in addition to OS.
High comorbidity burden is a common disease feature of CRPC patients, such as diabetes, heart failure, ischemic heart disease, etc.
A cohort study in the United States shows that comorbid cardiovascular disease is the second leading cause of death in prostate cancer patients. New endocrine therapies such as enzalutamide and abiraterone are the main options for the first-line treatment of mCRPC, and a meta-analysis showed that enzalutamide does not significantly increase cardiac risk compared with abiraterone.
The meta-analysis included two randomized, controlled, phase III clinical studies of enzalutamide and abiraterone in the treatment of mCRPC patients, aiming to evaluate the safety characteristics of the two drugs.
The results showed that the cardiac events and grade ≥3 cardiac events of the abiraterone combined with prednisone regimen were significantly higher than those of placebo; enzalutamide did not significantly increase the patients' cardiac events and grade ≥3 cardiac events.
In addition, glucocorticoid exposure has an increased potential risk of prostate cancer.
A retrospective analysis by Lowentritt et al.
showed that CRPC patients using glucocorticoids have a higher risk of clinical events.
Enzalutamide does not need to be combined with glucocorticoids, and in the above-mentioned American real-world study, when mCRPC patients with arrhythmia, congestive heart failure and type 2 diabetes, the proportion of patients receiving enzalutamide treatment is higher.
This reflects that doctors in the real world recognize the safety of enzalutamide more.
In terms of metastasis sites, different metastasis sites can benefit from different drugs.
Patients with lymph node metastasis, bone metastasis and visceral metastasis can all benefit from enzalutamide and docetaxel, while abiraterone is not suitable for patients with visceral metastases, and radium-223 is only suitable for patients with bone metastases.
In the CSCO Guidelines for Diagnosis and Treatment of Prostate Cancer (2020) for the first-line treatment of nmCRPC, enzalutamide, apatamide and dalotamide are recommended for the first-line treatment of nmCRPC, of which dalotamide is not marketed in China.
The 2020 ASCO conference reported the results of the PROSPER, SPARTAN and ARAMIS studies, and the results showed that the OS trends of the three drugs were similar (not a head-to-head study).
Professor Han said that for the judgment of nmCRPC research results, we cannot rely on OS alone.
The results of metastasis-free survival (MFS) are more meaningful.
An indirect meta-analysis showed that the MFS of enzalutamide and apatamide is better than dalotamide.
Figure 4 Results of indirect comparison of enzalutamide, apatamide and dalotamide.
Of course, safety and quality of life considerations are equally important.
Based on existing data, the adverse events related data of the above three drugs are similar, but apatamide can increase the incidence of skin rash and hypothyroidism.
Overall, enzalutamide is an ideal solution for the first-line treatment of CRPC patients.
At present, the National Medical Products Administration (NMPA) has approved enzalutamide for the treatment of nmCRPC and mCRPC, and mHSPC related research is also being gradually carried out.
The indications of enzalutamide are constantly advancing, becoming an effective "helper" for urological oncologists.
Source: "Explore Xintiandi" WeChat public account
As the disease progresses, most of them will turn into castration-resistant prostate cancer (CRPC).
Therefore, the treatment of CRPC is a hot topic for urological oncologists.
On January 9, 2021, the 2021 New World Forum on Genitourinary Tumor and Enzalutamide Non-metastatic Castration-Resistant Prostate Cancer (nmCRPC) China Listing Conference was successfully held in Zhuhai.
In this meeting, Professor Han Bangmin from Shanghai First People's Hospital discussed how to measure the comprehensive benefits of first-line treatment for CRPC patients.
Pay attention to the first-line options of mCRPC treatment options ranging from localized/locally advanced prostate cancer, to metastatic hormone-sensitive prostate cancer (mHSPC), and then to CRPC.
There are different systemic treatment strategies for each stage of advanced prostate cancer.
Professor Han said that considering that less than 50% of mCRPC patients can receive second-line treatment, the mCRPC treatment plan should be placed on the first line.
The Chinese Society of Clinical Oncology (CSCO) Guidelines for Diagnosis and Treatment of Prostate Cancer (2020) recommend that the first-line treatment options for mCRPC include enzalutamide, abiraterone, docetaxel and radium-223.
The TAX-327 study confirmed for the first time that docetaxel has a survival benefit in the treatment of mCRPC patients, and the use of new endocrine therapy to replace docetaxel as a first-line treatment is gradually increasing.
A retrospective study analyzed data from the Veterans Health Administration (VA) database and included 3637 patients diagnosed with mCRPC from January 2006 to August 2015, and evaluated Epoch1 (from 2006 to 2010, 83% of patients were first-line The treatment was docetaxel chemotherapy) and Epoch2 (from 2011 to 2016, 62% of patients were treated with enzalutamide or abiraterone as first-line treatment) time to biochemical progression and OS.
The results showed that compared with Epoch1, Epoch2's time to biochemical progression (13 vs 9 months) and OS (23 vs 15 months) were both prolonged.
Figure 1.
Results of Epoch1 and Epoch2 The PREVALIL study and the COU-AA-302 study respectively confirmed that enzalutamide and abiraterone have OS benefits for mCRPC patients.
The PREVAIL study showed that enzalutamide significantly prolonged OS by 4 months compared with placebo group (35.
3 vs 31.
3 months); COU-AA-302 study showed that abiraterone combined with prednisone prolonged OS by 4.
4 months compared with placebo group (34.
7 vs 30.
3 months).
It is worth noting that, in the absence of head-to-head data, in real-world studies in Europe and America, enzalutamide has additional OS benefits compared to abiraterone: an American real-world study retrospectively analyzed data from the VA database , To compare the OS benefit of mCRPC patients receiving first-line enzalutamide or abiraterone, compared to the sequential regimen of bicalutamide after treatment for >90 days.
The results showed that compared with the first-line abiraterone cohort, patients receiving enzalutamide had an 11% lower risk of death and better OS.
Figure 2 Results of a real-world study in the United States A French real-world study used the French National Health Data System to directly compare the OS of mCRPC patients who had not received chemotherapy before using enzalutamide or abiraterone.
The results show that, compared with abiraterone, enzalutamide has a 10% OS advantage.
Figure 3 French real-world study results weighing appropriate patients with mCRPC first-line program Professor Han proposed that the choice of first-line treatment for mCRPC patients requires consideration of basic comorbidities, metastatic load/site, Gleason score, etc.
, in addition to OS.
High comorbidity burden is a common disease feature of CRPC patients, such as diabetes, heart failure, ischemic heart disease, etc.
A cohort study in the United States shows that comorbid cardiovascular disease is the second leading cause of death in prostate cancer patients. New endocrine therapies such as enzalutamide and abiraterone are the main options for the first-line treatment of mCRPC, and a meta-analysis showed that enzalutamide does not significantly increase cardiac risk compared with abiraterone.
The meta-analysis included two randomized, controlled, phase III clinical studies of enzalutamide and abiraterone in the treatment of mCRPC patients, aiming to evaluate the safety characteristics of the two drugs.
The results showed that the cardiac events and grade ≥3 cardiac events of the abiraterone combined with prednisone regimen were significantly higher than those of placebo; enzalutamide did not significantly increase the patients' cardiac events and grade ≥3 cardiac events.
In addition, glucocorticoid exposure has an increased potential risk of prostate cancer.
A retrospective analysis by Lowentritt et al.
showed that CRPC patients using glucocorticoids have a higher risk of clinical events.
Enzalutamide does not need to be combined with glucocorticoids, and in the above-mentioned American real-world study, when mCRPC patients with arrhythmia, congestive heart failure and type 2 diabetes, the proportion of patients receiving enzalutamide treatment is higher.
This reflects that doctors in the real world recognize the safety of enzalutamide more.
In terms of metastasis sites, different metastasis sites can benefit from different drugs.
Patients with lymph node metastasis, bone metastasis and visceral metastasis can all benefit from enzalutamide and docetaxel, while abiraterone is not suitable for patients with visceral metastases, and radium-223 is only suitable for patients with bone metastases.
In the CSCO Guidelines for Diagnosis and Treatment of Prostate Cancer (2020) for the first-line treatment of nmCRPC, enzalutamide, apatamide and dalotamide are recommended for the first-line treatment of nmCRPC, of which dalotamide is not marketed in China.
The 2020 ASCO conference reported the results of the PROSPER, SPARTAN and ARAMIS studies, and the results showed that the OS trends of the three drugs were similar (not a head-to-head study).
Professor Han said that for the judgment of nmCRPC research results, we cannot rely on OS alone.
The results of metastasis-free survival (MFS) are more meaningful.
An indirect meta-analysis showed that the MFS of enzalutamide and apatamide is better than dalotamide.
Figure 4 Results of indirect comparison of enzalutamide, apatamide and dalotamide.
Of course, safety and quality of life considerations are equally important.
Based on existing data, the adverse events related data of the above three drugs are similar, but apatamide can increase the incidence of skin rash and hypothyroidism.
Overall, enzalutamide is an ideal solution for the first-line treatment of CRPC patients.
At present, the National Medical Products Administration (NMPA) has approved enzalutamide for the treatment of nmCRPC and mCRPC, and mHSPC related research is also being gradually carried out.
The indications of enzalutamide are constantly advancing, becoming an effective "helper" for urological oncologists.
Source: "Explore Xintiandi" WeChat public account
