-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
- Cosmetic Ingredient
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
*Only for medical professionals to read for reference, a new generation of androgen receptor inhibitor apatamide brings new breakthroughs to prostate cancer! The term "prostate cancer" is a nightmare for men.
As the most common malignant tumor of the reproductive system in European and American men, its mortality rate ranks second among male cancer deaths.
Although the incidence of prostate cancer in my country is lower than that of European and American countries, its incidence has shown a sustained and rapid increase in recent years [1].
With the continuous development of new drugs, the treatment of prostate cancer finally has a decisive opportunity.
Delaying the progression of the disease to mCRPC, a new generation of androgen receptor inhibitors has done it! Prostate cancer is generally a localized disease at the onset of the disease.
After biochemical recurrence, it enters metastatic hormone-sensitive prostate cancer (mHSPC) or non-metastatic castration-resistant prostate cancer (NM-CRPC), and finally enters metastatic castration-resistant by different routes.
Prostate cancer (mCRPC).
Once the disease progresses to the mCRPC stage, its annual rate of progression will reach 74%, and the annual mortality rate will be as high as 56% [2].
The NM-CRPC and mHSPC stages are the key turning points in delaying the progression and deterioration of prostate cancer! Therefore, blocking metastasis is essential for the treatment of advanced prostate cancer.
At the same time, if active treatment can be taken in the earlier mHSPC stage to prevent the disease from entering the mCRPC stage, the survival benefit of patients will be greatly improved.
The reactivation of the androgen receptor (AR) signaling pathway is a key driving factor for the progress of CRPC, and inhibition of the AR pathway is a very potential therapeutic pathway.
Along this line of thinking, a variety of AR inhibitors have been developed clinically, such as bicalutamide and enzalutamide.
However, their efficacy and safety are not good, and they cannot bring sufficient benefits to patients.
Therefore, NM-CRPC patients urgently need a new generation of therapeutic drugs.
A new generation of non-steroidal AR inhibitor apatamide is an ideal AR inhibitor, with higher AR affinity and good tolerability, and its indications are high-risk NM-CRPC and "all types" mHSPC, more Suitable for early use of diseases.
"Equipment" is upgraded, and apatamide becomes the preferred drug of the era.
In 2012, the second-generation non-steroidal AR inhibitor enzalutamide was launched in the United States, bringing hope to many prostate cancer patients.
But soon enzalutamide was found to have a higher degree of blood-brain barrier penetration, which is easier to inhibit GABA-A receptors, and can induce seizures [3].
■ Structural upgrade When patients constantly weighed the efficacy and side effects of enzalutamide, a new generation of non-steroidal AR inhibitor apatamide appeared.
It is worth mentioning that apatamide is the product of enzalutamide molecular structure optimization, which significantly reduces central toxicity and the risk of seizures.
The researchers replaced the phenyl group with a pyridyl group to optimize the general active group of non-steroidal AR inhibitors.
The optimized structure of the molecule has increased polarity and reduced ability to penetrate the blood-brain barrier, thereby successfully reducing central toxicity and seizures.
Risk [4].
Compared with enzalutamide, apatamide is more likely to accumulate in tumor tissues, while the concentration of brain tissue is only 1/4 of enzalutamide.
The steady-state level of apatamide is 2 to 4 times lower than that of enzalutamide, while the intratumoral level is comparable, with a higher tumor/plasma ratio.
In other words, at the same dose, apatamide is easier to achieve therapeutic effects, and the risk of neurological adverse events such as epilepsy is lower [3].
Concentration accumulation of apatamide and enzalutamide In addition, enzalutamide has no evidence of AR protection, and early use may induce AR resistance in advance and affect the clinical benefit of patients with sequential treatment.
Like the first-generation non-steroidal AR inhibitor bicalutamide, enzalutamide will also change from an AR inhibitor to an AR agonist [5], which has a great impact on patient treatment.
Apataamide can protect the AR axis, and the first-line treatment of NM-CRPC and mHSPC does not affect the subsequent NHT benefits [6], and the patient benefits are more significant.
■ In terms of efficacy upgrade, the Phase III data of the SPARTAN clinical trial showed that [7], the metastasis-free survival (MFS) of patients treated with apatamide was significantly improved, reaching 40.
51 months, compared with placebo treatment (16.
20 months) Extending more than two years, the risk of distant metastasis or death was reduced by 72%.
Other efficacy endpoints include statistically significant improvement in time to metastasis, progression-free survival (PFS), and time to symptom progression.
It can be seen that compared with enzalutamide, apatamide provides an effective treatment plan for NM-CRPC patients to delay disease progression, help patients achieve long-term survival with tumors, and bring practical comfort to patients and their families.
.
In addition, the results of the SPARTAN study also showed that 93% of patients with prostate-specific antigen (PSA) decreased by at least 50% from baseline, and the median time to a 50% decrease in PSA was 0.
95 months.
It can be seen that apatamide has brought a brand new option for the clinical treatment of high-risk NM-CRPC patients.
While delaying the progression of high-risk NM-CRPC patients, it also improved the quality of life of patients.
In the treatment of mHSPC, apatamide also shows an absolute advantage.
The TITAN study [8] suggested that early application of apatamide combined with androgen deprivation therapy (ADT) in the mHSPC disease stage can bring greater survival benefits to patients and effectively reduce the patient’s second disease progression or death risks of.
Compared with the control group, the risk of imaging progression or death in the apatamide treatment group was reduced by 52%, and the patient's imaging progression-free survival (rPFS) was significantly improved.
At baseline, patients with only bone metastases had a 62% reduction in the risk of progression or death in combination with apatamide, and patients with low tumor burden had a 64% reduction in the risk of progression or death in combination with apatamide.
It can be said that the TITAN study officially opened a new chapter in mHSPC treatment.
■ Safety upgrade In terms of safety, compared with enzalutamide, apatamide has a 66.
9% possibility of reducing the occurrence of adverse events (AE), and a 90.
9% possibility of reducing the occurrence of serious AEs.
In fatigue, hypertension The AE aspect is particularly remarkable.
Compared with enzalutamide patients, apatamide is more likely to have a better quality of life (HRQoL) from multiple angles such as FACT-P, FACT-G, PCSP, and PWB [9].
■ More preferred NM-CRPC comes from a meta-analysis conducted by Sun Yat-sen University Cancer Hospital [10]: For MFS and PSA-PFS, apatamide is a better drug for the treatment of NM-CRPC.
The study used a network meta-analysis to compare the efficacy of multiple drugs on NM-CRPC at the same time, and at the same time, it analyzed a combination of direct evidence in trials and indirect evidence between trials to evaluate the treatment effect.
This research reflects the important therapeutic value of apatamide in the field of NM-CRPC.
For MFS, apatamide is the preferred solution.
For PSA-PFS, apatamide is the preferred solution.
After upgrading, the molecular structure of apatamide is more polar and it is not easy to penetrate the blood-brain barrier.
The optimized structure of the molecule has increased polarity and decreased ability to penetrate the blood-brain barrier, thereby reducing central toxicity and the risk of seizures.
At the same time, it can be seen that apatamide is very effective in all dimensions of the disease, and it has AR protection evidence, and its safety is better, especially in terms of central nervous system adverse events and AE-related mortality.
.
Opening up the new era of NM-CRPC and mHSPC endocrine therapy The decisive opportunity for prostate cancer treatment is to effectively delay the progression of NM-CRPC and mHSPC to mCRPC, and a new generation of AR inhibitor apatamide with dual indications can accurately control its treatment From the perspective of medication experience and guideline recommendations, the current apatamide is more suitable for patients with early disease.
After upgrading, a new generation of AR inhibitor apatamide has brought good survival benefits for prostate cancer patients.
Based on its excellent efficacy, on September 5, 2019, apatamide was approved for marketing in China.
It is the first international/domestic drug to be approved for the treatment of NM-CRPC, filling the domestic and foreign treatment gap.
On August 12, 2020, apatamide was approved for the treatment of mHSPC, becoming the only drug for "all types" of mHSPC, which can be said to open a new era of NM-CRPC and mHSPC endocrine therapy.
I believe that as more research data is announced, apatamide will benefit a wider range of prostate cancer patients in the future.
Expert ProfileProfessor Lu Jiaju, Director, Chief Physician, Professor, and Doctoral Tutor of Urology, Shandong Provincial Hospital, Deputy Director, Urology Branch, Shandong Medical Association, Deputy Director, Urology Branch, Shandong Medical Association, Deputy Director, Medical Robot Branch, Shandong Medical Association Member of the Standing Committee of the Prostate Cancer Expert Committee of the Chinese Society of Clinical Oncology Member of the Urology Branch of the Chinese Medical Doctors Association Member of the Committee of Urology and Male Reproductive Tumors of the Chinese Anti-Cancer Association Member of the Urology Branch of the Chinese Society of Integrated Traditional Chinese and Western Medicine Member of the Standing Committee of the Urology Branch of the Shandong Anticancer Association Shandong Province Vice Chairman of the Urology Branch of the Chinese and Western Medicine Association "Chinese Journal of Andrology" Editorial member of "Journal of Shandong University" (Medical Edition) "Journal of Minimally Invasive Urology" Professor Zhang Yangang Director of Department of Urology, Shanxi Bethune Hospital, Doctor of Medicine, Master supervisor, chief physician, National Committee of Urology Committee, Chinese Medical Association, National Committee of Surgical Engineering and Transformation Group, Chinese Medical Engineering Branch, Chinese Medical Association, National Committee, National Committee of Urinary and Male Reproductive Tumor Professional Committee, Chinese Anti-Cancer Association Member of the 1st Urology Professional Committee Vice Chairman of the Urology Professional Committee of Shanxi Medical Association Vice Chairman of the Urinary Male Reproductive Tumor Professional Committee of Shanxi Anticancer Association Vice Chairman of the Urology Branch of Shanxi Medical Doctors Association Vice Chairman of Shanxi Medical Doctors Association Andrology and Sex Vice-Chairman of the First Committee of the Medical Physician Branch Chairman of the Professional Committee of the Third Sexual Society of Shanxi Provincial Society National Committee of the Urology Professional Committee of the Chinese Research Hospital Association Deputy Chairman of the Expert Committee of China Prostate Treatment and Rehabilitation Technology Innovation Alliance Member of the Standing Committee of the Professional Committee of Adolescent Health and Medicine of the Association, Member of the First Committee of Urology Professional Committee of Shanxi Association of Integrated Traditional Chinese and Western Medicine, Member of the First Committee of Organ Transplant Doctor Branch of Shanxi Medical Association, Member of the First Committee of Urology Specialist Admission Committee of the Ministry of Health, Shanxi Expert Group Member Taiyuan Medical Association Medical Malpractice Technical Appraisal Expert Database Member Shanxi Provincial Labor Ability Appraisal Medical and Health Committee Expert Reference: [1] Liu Jianping, Wang He.
New progress in immunotherapy for castration-resistant prostate cancer [J].
Chinese Journal of Surgery, 2016, 54 (10): 787-791.
[2] Lee CH, Kantoff P.
Treatment of Metastatic Prostate Cancer in 2018JAMA Oncol 2019; 5 (2): 263-264; doi: 10.
1001/jamaoncol.
2018.
As the most common malignant tumor of the reproductive system in European and American men, its mortality rate ranks second among male cancer deaths.
Although the incidence of prostate cancer in my country is lower than that of European and American countries, its incidence has shown a sustained and rapid increase in recent years [1].
With the continuous development of new drugs, the treatment of prostate cancer finally has a decisive opportunity.
Delaying the progression of the disease to mCRPC, a new generation of androgen receptor inhibitors has done it! Prostate cancer is generally a localized disease at the onset of the disease.
After biochemical recurrence, it enters metastatic hormone-sensitive prostate cancer (mHSPC) or non-metastatic castration-resistant prostate cancer (NM-CRPC), and finally enters metastatic castration-resistant by different routes.
Prostate cancer (mCRPC).
Once the disease progresses to the mCRPC stage, its annual rate of progression will reach 74%, and the annual mortality rate will be as high as 56% [2].
The NM-CRPC and mHSPC stages are the key turning points in delaying the progression and deterioration of prostate cancer! Therefore, blocking metastasis is essential for the treatment of advanced prostate cancer.
At the same time, if active treatment can be taken in the earlier mHSPC stage to prevent the disease from entering the mCRPC stage, the survival benefit of patients will be greatly improved.
The reactivation of the androgen receptor (AR) signaling pathway is a key driving factor for the progress of CRPC, and inhibition of the AR pathway is a very potential therapeutic pathway.
Along this line of thinking, a variety of AR inhibitors have been developed clinically, such as bicalutamide and enzalutamide.
However, their efficacy and safety are not good, and they cannot bring sufficient benefits to patients.
Therefore, NM-CRPC patients urgently need a new generation of therapeutic drugs.
A new generation of non-steroidal AR inhibitor apatamide is an ideal AR inhibitor, with higher AR affinity and good tolerability, and its indications are high-risk NM-CRPC and "all types" mHSPC, more Suitable for early use of diseases.
"Equipment" is upgraded, and apatamide becomes the preferred drug of the era.
In 2012, the second-generation non-steroidal AR inhibitor enzalutamide was launched in the United States, bringing hope to many prostate cancer patients.
But soon enzalutamide was found to have a higher degree of blood-brain barrier penetration, which is easier to inhibit GABA-A receptors, and can induce seizures [3].
■ Structural upgrade When patients constantly weighed the efficacy and side effects of enzalutamide, a new generation of non-steroidal AR inhibitor apatamide appeared.
It is worth mentioning that apatamide is the product of enzalutamide molecular structure optimization, which significantly reduces central toxicity and the risk of seizures.
The researchers replaced the phenyl group with a pyridyl group to optimize the general active group of non-steroidal AR inhibitors.
The optimized structure of the molecule has increased polarity and reduced ability to penetrate the blood-brain barrier, thereby successfully reducing central toxicity and seizures.
Risk [4].
Compared with enzalutamide, apatamide is more likely to accumulate in tumor tissues, while the concentration of brain tissue is only 1/4 of enzalutamide.
The steady-state level of apatamide is 2 to 4 times lower than that of enzalutamide, while the intratumoral level is comparable, with a higher tumor/plasma ratio.
In other words, at the same dose, apatamide is easier to achieve therapeutic effects, and the risk of neurological adverse events such as epilepsy is lower [3].
Concentration accumulation of apatamide and enzalutamide In addition, enzalutamide has no evidence of AR protection, and early use may induce AR resistance in advance and affect the clinical benefit of patients with sequential treatment.
Like the first-generation non-steroidal AR inhibitor bicalutamide, enzalutamide will also change from an AR inhibitor to an AR agonist [5], which has a great impact on patient treatment.
Apataamide can protect the AR axis, and the first-line treatment of NM-CRPC and mHSPC does not affect the subsequent NHT benefits [6], and the patient benefits are more significant.
■ In terms of efficacy upgrade, the Phase III data of the SPARTAN clinical trial showed that [7], the metastasis-free survival (MFS) of patients treated with apatamide was significantly improved, reaching 40.
51 months, compared with placebo treatment (16.
20 months) Extending more than two years, the risk of distant metastasis or death was reduced by 72%.
Other efficacy endpoints include statistically significant improvement in time to metastasis, progression-free survival (PFS), and time to symptom progression.
It can be seen that compared with enzalutamide, apatamide provides an effective treatment plan for NM-CRPC patients to delay disease progression, help patients achieve long-term survival with tumors, and bring practical comfort to patients and their families.
.
In addition, the results of the SPARTAN study also showed that 93% of patients with prostate-specific antigen (PSA) decreased by at least 50% from baseline, and the median time to a 50% decrease in PSA was 0.
95 months.
It can be seen that apatamide has brought a brand new option for the clinical treatment of high-risk NM-CRPC patients.
While delaying the progression of high-risk NM-CRPC patients, it also improved the quality of life of patients.
In the treatment of mHSPC, apatamide also shows an absolute advantage.
The TITAN study [8] suggested that early application of apatamide combined with androgen deprivation therapy (ADT) in the mHSPC disease stage can bring greater survival benefits to patients and effectively reduce the patient’s second disease progression or death risks of.
Compared with the control group, the risk of imaging progression or death in the apatamide treatment group was reduced by 52%, and the patient's imaging progression-free survival (rPFS) was significantly improved.
At baseline, patients with only bone metastases had a 62% reduction in the risk of progression or death in combination with apatamide, and patients with low tumor burden had a 64% reduction in the risk of progression or death in combination with apatamide.
It can be said that the TITAN study officially opened a new chapter in mHSPC treatment.
■ Safety upgrade In terms of safety, compared with enzalutamide, apatamide has a 66.
9% possibility of reducing the occurrence of adverse events (AE), and a 90.
9% possibility of reducing the occurrence of serious AEs.
In fatigue, hypertension The AE aspect is particularly remarkable.
Compared with enzalutamide patients, apatamide is more likely to have a better quality of life (HRQoL) from multiple angles such as FACT-P, FACT-G, PCSP, and PWB [9].
■ More preferred NM-CRPC comes from a meta-analysis conducted by Sun Yat-sen University Cancer Hospital [10]: For MFS and PSA-PFS, apatamide is a better drug for the treatment of NM-CRPC.
The study used a network meta-analysis to compare the efficacy of multiple drugs on NM-CRPC at the same time, and at the same time, it analyzed a combination of direct evidence in trials and indirect evidence between trials to evaluate the treatment effect.
This research reflects the important therapeutic value of apatamide in the field of NM-CRPC.
For MFS, apatamide is the preferred solution.
For PSA-PFS, apatamide is the preferred solution.
After upgrading, the molecular structure of apatamide is more polar and it is not easy to penetrate the blood-brain barrier.
The optimized structure of the molecule has increased polarity and decreased ability to penetrate the blood-brain barrier, thereby reducing central toxicity and the risk of seizures.
At the same time, it can be seen that apatamide is very effective in all dimensions of the disease, and it has AR protection evidence, and its safety is better, especially in terms of central nervous system adverse events and AE-related mortality.
.
Opening up the new era of NM-CRPC and mHSPC endocrine therapy The decisive opportunity for prostate cancer treatment is to effectively delay the progression of NM-CRPC and mHSPC to mCRPC, and a new generation of AR inhibitor apatamide with dual indications can accurately control its treatment From the perspective of medication experience and guideline recommendations, the current apatamide is more suitable for patients with early disease.
After upgrading, a new generation of AR inhibitor apatamide has brought good survival benefits for prostate cancer patients.
Based on its excellent efficacy, on September 5, 2019, apatamide was approved for marketing in China.
It is the first international/domestic drug to be approved for the treatment of NM-CRPC, filling the domestic and foreign treatment gap.
On August 12, 2020, apatamide was approved for the treatment of mHSPC, becoming the only drug for "all types" of mHSPC, which can be said to open a new era of NM-CRPC and mHSPC endocrine therapy.
I believe that as more research data is announced, apatamide will benefit a wider range of prostate cancer patients in the future.
Expert ProfileProfessor Lu Jiaju, Director, Chief Physician, Professor, and Doctoral Tutor of Urology, Shandong Provincial Hospital, Deputy Director, Urology Branch, Shandong Medical Association, Deputy Director, Urology Branch, Shandong Medical Association, Deputy Director, Medical Robot Branch, Shandong Medical Association Member of the Standing Committee of the Prostate Cancer Expert Committee of the Chinese Society of Clinical Oncology Member of the Urology Branch of the Chinese Medical Doctors Association Member of the Committee of Urology and Male Reproductive Tumors of the Chinese Anti-Cancer Association Member of the Urology Branch of the Chinese Society of Integrated Traditional Chinese and Western Medicine Member of the Standing Committee of the Urology Branch of the Shandong Anticancer Association Shandong Province Vice Chairman of the Urology Branch of the Chinese and Western Medicine Association "Chinese Journal of Andrology" Editorial member of "Journal of Shandong University" (Medical Edition) "Journal of Minimally Invasive Urology" Professor Zhang Yangang Director of Department of Urology, Shanxi Bethune Hospital, Doctor of Medicine, Master supervisor, chief physician, National Committee of Urology Committee, Chinese Medical Association, National Committee of Surgical Engineering and Transformation Group, Chinese Medical Engineering Branch, Chinese Medical Association, National Committee, National Committee of Urinary and Male Reproductive Tumor Professional Committee, Chinese Anti-Cancer Association Member of the 1st Urology Professional Committee Vice Chairman of the Urology Professional Committee of Shanxi Medical Association Vice Chairman of the Urinary Male Reproductive Tumor Professional Committee of Shanxi Anticancer Association Vice Chairman of the Urology Branch of Shanxi Medical Doctors Association Vice Chairman of Shanxi Medical Doctors Association Andrology and Sex Vice-Chairman of the First Committee of the Medical Physician Branch Chairman of the Professional Committee of the Third Sexual Society of Shanxi Provincial Society National Committee of the Urology Professional Committee of the Chinese Research Hospital Association Deputy Chairman of the Expert Committee of China Prostate Treatment and Rehabilitation Technology Innovation Alliance Member of the Standing Committee of the Professional Committee of Adolescent Health and Medicine of the Association, Member of the First Committee of Urology Professional Committee of Shanxi Association of Integrated Traditional Chinese and Western Medicine, Member of the First Committee of Organ Transplant Doctor Branch of Shanxi Medical Association, Member of the First Committee of Urology Specialist Admission Committee of the Ministry of Health, Shanxi Expert Group Member Taiyuan Medical Association Medical Malpractice Technical Appraisal Expert Database Member Shanxi Provincial Labor Ability Appraisal Medical and Health Committee Expert Reference: [1] Liu Jianping, Wang He.
New progress in immunotherapy for castration-resistant prostate cancer [J].
Chinese Journal of Surgery, 2016, 54 (10): 787-791.
[2] Lee CH, Kantoff P.
Treatment of Metastatic Prostate Cancer in 2018JAMA Oncol 2019; 5 (2): 263-264; doi: 10.
1001/jamaoncol.
2018.
