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*Only for medical professionals to read for reference.
Is the real-world study of Chidamide in the treatment of breast cancer consistent with clinical research benefits? On April 9-10, 2021, the 2021 National Breast Cancer Conference and the Chinese Society of Clinical Oncology (CSCO) Breast Cancer Annual Meeting were officially held in Beijing, which is waning in spring.
In the hormone receptor positive (HR+) breast cancer session, Professor Sun Tao from Liaoning Cancer Hospital brought a summary of the staged data of the Real World Study (RWS) of Chidamide.
The "Medical Oncology Channel" summarized the themes reported by Professor Sun for readers.
Prof.
Tao Sun reported on site Chidamide for HR+ advanced breast cancer initial exploration Chidamide is a local original research drug in my country and the world's first subtype selective histone deacetylase oral inhibitor (HDACi) approved for marketing , It was first approved in the treatment of peripheral T-cell lymphoma, and its exploration in solid tumors is also expanding.
Although the non-specific anti-tumor mechanism of Chidamide has been confirmed, it has a unique mechanism of action for hormone receptor positive (HR+) breast cancer.
▌ The mechanism of action of Chidamide against HR+ breast cancer: 1.
Inhibit the alternative growth factor signaling pathway: by down-regulating the phosphorylation of growth factor receptor pathway related proteins (such as PI3K/AKT/mTOR and Raf/MEK/ERK) The activation of estrogen receptor (ER), and by increasing the acetylation level of heat shock protein 90 (HSP90) to induce ER degradation, thereby inhibiting the hormone-independent activation pathway.
2.
By increasing the level of lysine acetylation at certain sites in the ER, it directly inhibits the hormone-dependent activation pathway.
Based on this, the clinical exploration of Chidamide for the treatment of HR+ advanced breast cancer has begun.
In exploratory clinical studies, it was found that the treatment with chidamide combined with exemestane was well tolerated, and the safety events were similar and controllable to that of monotherapy.
The median progression-free survival of 20 subjects was The period (PFS) was 7.
6 months, and the objective response rate was 20%.
The results support the follow-up clinical trials of chidamide combined with exemestane in HR+ advanced breast cancer patients.
▌ The phase III clinical trial of chidamide combined with exemestane in the treatment of HR+ advanced breast cancer.
Due to the above results, the combination of chidamide and exemestane in the treatment of advanced HR+ The phase III clinical trial ACE for breast cancer came into being.
Figure 1 ACE study design The results of the ACE study showed that the Chidamide combination group significantly prolonged PFS (9.
2 months vs 3.
8 months, P=0.
024).
In the subgroup analysis, people with visceral metastases, previous use of non-steroidal aromatase inhibitors (AI), and progesterone receptor (PR) negative people all benefited better.
The ACE results were reported by Professor Jiang Zefei at the 2018 European Society of Medical Oncology (ESMO) conference and published in the full text of The Lancet Oncology.
Chidamide is used for HR+, HER2- advanced breast The positive results of cancer treatment were announced to the world.
In 2019, the indication for breast cancer of Chidamide was approved: combined with AI for HR+, HER2-, postmenopausal, locally advanced or metastatic breast cancer patients who have relapsed or progressed through endocrine therapy.
However, the ACE study still has unanswered clinical questions, such as the best timing of chidamide and the dominant population, and is the use of CDK4/6i effective in patients with failed CDK4/6i? All these require real-world studies to further verify the efficacy and safety of chidamide combination therapy.
The real world study of chidamide, Professor Zefei Jiang and Professor Qingyuan Zhang from the Affiliated Tumor Hospital of Harbin Medical University led this multi-center, prospective, non-randomized, and open real world study (RWS).
The study allowed patients who had failed treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and mammalian target of rapamycin inhibitors (mTORi) to be included in the group.
There are two treatment options for patients, namely Cedar This amine + Fulvestrant and Chidamide + AI.
Figure 2 In the phased data of the real-world study design of Cedarbenamine as of March 16, 2021, the two sub-programs collected a total of 505 valid data.
Among the patients enrolled in the study, 51% of patients had visceral metastases, and more than 80% of those who used chidamide ≥ 1 line.
Table 1 Baseline characteristics of patients in the real-world study Based on phased data, the overall population's complete remission (CR) + partial remission (PR) rate was 12%, the disease stable (SD) rate was 67.
9%, and the overall PFS was 6.
4 months.
Figure 3 The median PFS of the two sub-programs of the real-world study of short-term efficacy was 8.
7 months and 6.
1 months, respectively, and there was no significant difference between the groups.
The median PFS of the overall population without visceral metastasis and visceral metastasis was 9.
7 and 4.
9 months, respectively, and there were significant differences between the groups.
According to the number of lines used, the median PFS of patients treated with chidamide was 15.
4 months for the first-line treatment; 7.
4 months for the second-line treatment and 5.
0 months for the third-line treatment.
P<0.
01 between the first-line, second-line, and third-line groups, there is a significant difference.
This reminds us that the benefit of front-line treatment with Chidamide is greater.
In addition, the results showed that the median PFS of patients who had never used rescue chemotherapy and had used rescue chemotherapy were 8.
2 months and 5.
2 months, respectively, and there was a significant difference between the groups.
The median PFS of the previous treatment failure with CDK4/6 inhibitor and CDK4/6 inhibitor was 8.
7 months and 4.
2 months, respectively, and there was a significant difference between the groups.
For patients who have previously received CDK4/6 inhibitor therapy, the second and third-line use of Chidamide, the median PFS is 5.
1 months, and the 6-month progression-free survival rate is 45%, which is in line with the result of the BYLieve study of 50.
4% very similar. In the case that PI3K inhibitors are not yet on the market, Chidamide may be a better choice.
In terms of safety, the adverse events of the two groups were similar.
Decrease in neutrophil count and decreased platelet count were the most common adverse reactions.
Other common adverse reactions included fatigue and gastrointestinal reactions, which occurred in grade 3/4 The rate is less than 5%, and the overall adverse reaction is similar to the ACE study.
Figure 4 The overall occurrence of adverse events in the real-world study.
Summary of the interim data from the real-world study of Chidamide: Preliminary data show that disease control is good, with a CR+PR rate of 11.
7%, and a median PFS of 6.
4 months; Patients who have used chemotherapy and have an earlier treatment line are more likely to benefit; the adverse reactions shown in the study are basically the same as those in the registered study ACE, and no unintended adverse reactions have been found.
How to strengthen the safety management of Chidamide? The Anti-Lymphoma Alliance of the Chinese Society of Clinical Oncology, the Anti-Leukemia Alliance of the Chinese Society of Clinical Oncology, and the Breast Cancer Expert Committee of the Chinese Society of Clinical Oncology jointly drafted the "Expert Consensus on the Management of Adverse Reactions of Chidamide", which is the rational use of Chidamide Adverse reaction management provides a reference, and it has entered the final review stage.
According to ACE research and real-world research, hematological adverse reactions are the most common adverse reactions.
For most patients, hematological adverse reactions can be restored to baseline levels in a short period of time by suspending the drug, and symptomatic treatment can be given.
Effective alleviation, so hematological adverse reactions are reversible and controllable, and the adverse reactions and management combined with targeted and immunotherapy need to accumulate more clinical data.
Summary: The real-world study of Chidamide further confirms its safety and effectiveness, and suggests that early-line treatment and patients who have not previously received chemotherapy have more significant benefits.
The overall safety of chidamide combination is controllable, and the promotion of the "Expert Consensus on the Management of Side Effects of Chidamide" will be conducive to the safety management of patients and the rational use of drugs.
Preliminary data show that chidamide combined with fulvestrant is safe and effective in the treatment of HR+ advanced breast cancer patients, which makes us look forward to further follow-up results.
Is the real-world study of Chidamide in the treatment of breast cancer consistent with clinical research benefits? On April 9-10, 2021, the 2021 National Breast Cancer Conference and the Chinese Society of Clinical Oncology (CSCO) Breast Cancer Annual Meeting were officially held in Beijing, which is waning in spring.
In the hormone receptor positive (HR+) breast cancer session, Professor Sun Tao from Liaoning Cancer Hospital brought a summary of the staged data of the Real World Study (RWS) of Chidamide.
The "Medical Oncology Channel" summarized the themes reported by Professor Sun for readers.
Prof.
Tao Sun reported on site Chidamide for HR+ advanced breast cancer initial exploration Chidamide is a local original research drug in my country and the world's first subtype selective histone deacetylase oral inhibitor (HDACi) approved for marketing , It was first approved in the treatment of peripheral T-cell lymphoma, and its exploration in solid tumors is also expanding.
Although the non-specific anti-tumor mechanism of Chidamide has been confirmed, it has a unique mechanism of action for hormone receptor positive (HR+) breast cancer.
▌ The mechanism of action of Chidamide against HR+ breast cancer: 1.
Inhibit the alternative growth factor signaling pathway: by down-regulating the phosphorylation of growth factor receptor pathway related proteins (such as PI3K/AKT/mTOR and Raf/MEK/ERK) The activation of estrogen receptor (ER), and by increasing the acetylation level of heat shock protein 90 (HSP90) to induce ER degradation, thereby inhibiting the hormone-independent activation pathway.
2.
By increasing the level of lysine acetylation at certain sites in the ER, it directly inhibits the hormone-dependent activation pathway.
Based on this, the clinical exploration of Chidamide for the treatment of HR+ advanced breast cancer has begun.
In exploratory clinical studies, it was found that the treatment with chidamide combined with exemestane was well tolerated, and the safety events were similar and controllable to that of monotherapy.
The median progression-free survival of 20 subjects was The period (PFS) was 7.
6 months, and the objective response rate was 20%.
The results support the follow-up clinical trials of chidamide combined with exemestane in HR+ advanced breast cancer patients.
▌ The phase III clinical trial of chidamide combined with exemestane in the treatment of HR+ advanced breast cancer.
Due to the above results, the combination of chidamide and exemestane in the treatment of advanced HR+ The phase III clinical trial ACE for breast cancer came into being.
Figure 1 ACE study design The results of the ACE study showed that the Chidamide combination group significantly prolonged PFS (9.
2 months vs 3.
8 months, P=0.
024).
In the subgroup analysis, people with visceral metastases, previous use of non-steroidal aromatase inhibitors (AI), and progesterone receptor (PR) negative people all benefited better.
The ACE results were reported by Professor Jiang Zefei at the 2018 European Society of Medical Oncology (ESMO) conference and published in the full text of The Lancet Oncology.
Chidamide is used for HR+, HER2- advanced breast The positive results of cancer treatment were announced to the world.
In 2019, the indication for breast cancer of Chidamide was approved: combined with AI for HR+, HER2-, postmenopausal, locally advanced or metastatic breast cancer patients who have relapsed or progressed through endocrine therapy.
However, the ACE study still has unanswered clinical questions, such as the best timing of chidamide and the dominant population, and is the use of CDK4/6i effective in patients with failed CDK4/6i? All these require real-world studies to further verify the efficacy and safety of chidamide combination therapy.
The real world study of chidamide, Professor Zefei Jiang and Professor Qingyuan Zhang from the Affiliated Tumor Hospital of Harbin Medical University led this multi-center, prospective, non-randomized, and open real world study (RWS).
The study allowed patients who had failed treatment with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and mammalian target of rapamycin inhibitors (mTORi) to be included in the group.
There are two treatment options for patients, namely Cedar This amine + Fulvestrant and Chidamide + AI.
Figure 2 In the phased data of the real-world study design of Cedarbenamine as of March 16, 2021, the two sub-programs collected a total of 505 valid data.
Among the patients enrolled in the study, 51% of patients had visceral metastases, and more than 80% of those who used chidamide ≥ 1 line.
Table 1 Baseline characteristics of patients in the real-world study Based on phased data, the overall population's complete remission (CR) + partial remission (PR) rate was 12%, the disease stable (SD) rate was 67.
9%, and the overall PFS was 6.
4 months.
Figure 3 The median PFS of the two sub-programs of the real-world study of short-term efficacy was 8.
7 months and 6.
1 months, respectively, and there was no significant difference between the groups.
The median PFS of the overall population without visceral metastasis and visceral metastasis was 9.
7 and 4.
9 months, respectively, and there were significant differences between the groups.
According to the number of lines used, the median PFS of patients treated with chidamide was 15.
4 months for the first-line treatment; 7.
4 months for the second-line treatment and 5.
0 months for the third-line treatment.
P<0.
01 between the first-line, second-line, and third-line groups, there is a significant difference.
This reminds us that the benefit of front-line treatment with Chidamide is greater.
In addition, the results showed that the median PFS of patients who had never used rescue chemotherapy and had used rescue chemotherapy were 8.
2 months and 5.
2 months, respectively, and there was a significant difference between the groups.
The median PFS of the previous treatment failure with CDK4/6 inhibitor and CDK4/6 inhibitor was 8.
7 months and 4.
2 months, respectively, and there was a significant difference between the groups.
For patients who have previously received CDK4/6 inhibitor therapy, the second and third-line use of Chidamide, the median PFS is 5.
1 months, and the 6-month progression-free survival rate is 45%, which is in line with the result of the BYLieve study of 50.
4% very similar. In the case that PI3K inhibitors are not yet on the market, Chidamide may be a better choice.
In terms of safety, the adverse events of the two groups were similar.
Decrease in neutrophil count and decreased platelet count were the most common adverse reactions.
Other common adverse reactions included fatigue and gastrointestinal reactions, which occurred in grade 3/4 The rate is less than 5%, and the overall adverse reaction is similar to the ACE study.
Figure 4 The overall occurrence of adverse events in the real-world study.
Summary of the interim data from the real-world study of Chidamide: Preliminary data show that disease control is good, with a CR+PR rate of 11.
7%, and a median PFS of 6.
4 months; Patients who have used chemotherapy and have an earlier treatment line are more likely to benefit; the adverse reactions shown in the study are basically the same as those in the registered study ACE, and no unintended adverse reactions have been found.
How to strengthen the safety management of Chidamide? The Anti-Lymphoma Alliance of the Chinese Society of Clinical Oncology, the Anti-Leukemia Alliance of the Chinese Society of Clinical Oncology, and the Breast Cancer Expert Committee of the Chinese Society of Clinical Oncology jointly drafted the "Expert Consensus on the Management of Adverse Reactions of Chidamide", which is the rational use of Chidamide Adverse reaction management provides a reference, and it has entered the final review stage.
According to ACE research and real-world research, hematological adverse reactions are the most common adverse reactions.
For most patients, hematological adverse reactions can be restored to baseline levels in a short period of time by suspending the drug, and symptomatic treatment can be given.
Effective alleviation, so hematological adverse reactions are reversible and controllable, and the adverse reactions and management combined with targeted and immunotherapy need to accumulate more clinical data.
Summary: The real-world study of Chidamide further confirms its safety and effectiveness, and suggests that early-line treatment and patients who have not previously received chemotherapy have more significant benefits.
The overall safety of chidamide combination is controllable, and the promotion of the "Expert Consensus on the Management of Side Effects of Chidamide" will be conducive to the safety management of patients and the rational use of drugs.
Preliminary data show that chidamide combined with fulvestrant is safe and effective in the treatment of HR+ advanced breast cancer patients, which makes us look forward to further follow-up results.
