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*Only for medical professionals to read for reference, 1 minute a day, to give you professional "talking information" in the tumor circle! (If you need the original text of the literature, you can add the editor WeChat yxj_oncology to obtain) Key points CCR: Anlotinib is safe and effective in the treatment of locally advanced or metastatic medullary thyroid cancer.
CCR: Androgen deprivation therapy combined with piperacillil does not improve RB-positive metastasis Sex hormone-sensitive prostate cancer prognosis JTO: Anti-PD-1 monoclonal antibody combination regimen has better survival results in the first-line treatment of advanced non-small cell lung cancer.
"O drug" combination therapy for the treatment of esophageal squamous cell carcinoma Phase III clinical study CheckMate-648 achieved positive results" The successful Phase III study of KEYNOTE-564 in the single-agent adjuvant treatment of renal cell carcinoma of K drug: Ametinib is used in the first-line treatment of NSCLC to be included in the breakthrough therapy 01CCR: Anlotinib is safe in the treatment of locally advanced or metastatic medullary thyroid cancer Effective April 8, the ALTER 01031 study reported by Clinical Cancer Research showed that Anlotinib is safe and effective in the treatment of locally advanced or metastatic medullary thyroid carcinoma (MTC).
Screenshot of the cover of the article Anlotinib is a new type of multi-target tyrosine kinase inhibitor that can target the targets VEGFR, PDGFR, FGFR and c-Kit.
This randomized, double-blind, phase IIB study aims to evaluate the efficacy and safety of Anlotinib in the treatment of MTC.
The study included patients with unresectable locally advanced or metastatic MTC confirmed by histopathology and randomly assigned to receive anlotinib (12 mg, qd, d1-14, every 3 weeks as a treatment cycle) or comfort at a 2:1 ratio Drug treatment; patients in the placebo group are allowed to receive open-label anlotinib treatment after the disease has progressed.
The primary endpoint is progression-free survival (PFS).
Secondary endpoints include objective response rate (ORR), disease control rate (DCR), and overall survival (OS).
The results showed that a total of 91 patients were enrolled.
The median PFS of the anlotinib group was significantly longer than that of the placebo group (20.
7 months vs 11.
1 months, HR 0.
53, P=0.
029).
The ORR of anlotinib treatment reached 48.
4%.
The incidence of treatment-related adverse events (TRAE) in the anlotinib group and placebo group was 100% and 89.
7%, respectively.
The most common TRAEs (all grades) in the Anlotinib group included palmoplantar sensory loss erythema syndrome (62.
9%), proteinuria (61.
3%), and hypertriglyceridemia (48.
4%).
The researchers pointed out that MTC accounts for about 2% of all thyroid cancers, and its prognosis is relatively poor compared with differentiated thyroid cancers.
In this phase IIB study, Anlotinib has shown good efficacy and safety in the treatment of MTC, and may become a new treatment option for this rare disease, especially for Chinese patients.
02CCR: Androgen deprivation treatment combined with piperacillide does not improve the prognosis of RB-positive metastatic hormone-sensitive prostate cancer.
On April 8, a randomized phase II study reported by Clinical Cancer Research showed that compared with androgen deprivation (AD) treatment, Pipercillil+AD treatment did not improve the prognosis of retinoblastoma gene (RB)-positive metastatic hormone-sensitive prostate cancer (mHSPC).
Screenshot of the cover of the article.
Piperacillil is a cyclin-dependent kinase (CDK) 4/6 inhibitor.
Preclinical prostate cancer model studies have shown that CDK4/6 can bind to cyclin D (cyclin D), activate RB to release the transcription factor E2F, promote the transcription of cell cycle-related genes, and make the cell enter the S phase.
CDK4/6i can effectively block the progression of tumor cells from G1 phase to S phase.
The study hypothesized that the combined targeting of the androgen receptor and cyclin would improve the prognosis of mHSPC patients.
The study included 60 RB-positive mHSPC patients who were randomly (1:2) divided into group 1 (AD) or group 2 (AD + piperacillil).
The primary endpoint is the prostate-specific antigen (PSA) remission rate (RR) after 28 weeks of treatment.
Secondary endpoints include safety, PSA level and clinical PFS and radiological RR.
Count circulating tumor cells (CTC) at various time points, and perform exome sequencing of tumors when feasible.
The results showed that a total of 72 mHSPC patients underwent metastatic disease biopsy.
64 patients had enough tissue for RB evaluation, of which 62 (97%) still had RB expression.
A total of 60 patients received treatment (group 1: 20 cases; group 2: 40 cases).
At 28 weeks, 80% of patients (group 1: 16/20, group 2: 32/40; P=0.
87) reached the primary PSA endpoint ≤ 4ng/mL, and the undetectable rates of PSA in group 1 and group 2 were respectively 50% and 43% (P=0.
5).
The radiological RR of group 1 and group 2 were both 89%, and the 12-month PSA-PFS rate (PSA progression-free survival) was 69% and 74%, respectively (P=0.
72).
Mutations in TP53 and PIK3 pathways, 8q copy number gain, and CTC before treatment are associated with decreased PSA-PFS.
In terms of safety, the most common grade 3/4 adverse event in Group 2 was neutropenia.
The researchers said that piperacillil failed to affect the prognosis of RB-positive mHSPC.
03JTO: The anti-PD-1 monoclonal antibody combination regimen has better survival results in the first-line treatment of advanced non-small cell lung cancer.
On April 8, a systematic review and network meta-analysis reported in the Journal of Thoracic Oncology showed that in advanced non-small cell lung cancer ( In the first-line immune combination therapy of NSCLC, the anti-programmed death molecule 1 (PD-1) combination program may have better survival results and comparable safety than the anti-programmed death ligand 1 (PD-L1) combination program Sex.
Screenshot of the cover of the article.
Although a series of randomized controlled trials on the first-line immune combination therapy for advanced NSCLC have studied different combinations, the best combination strategy has yet to be determined. To this end, the researchers searched PubMed, Embase, Cochrane library, ClinicalTrials.
gov, and related literature from large international conferences to conduct systematic reviews and Bayesian network meta-analysis to compare immunocombination therapy with other therapies for first-line treatment of patients with advanced NSCLC.
effect.
The results showed that a total of 16 studies were analyzed, involving 8,278 patients and 10 immunization combinations.
Pembrolizumab + chemotherapy, sintilizumab + chemotherapy can provide the best OS benefit (HR: 0.
96, 95% CI: 0.
72-1.
29).
Atelizumab + bevacizumab + chemotherapy seems to provide the best PFS (HR: 0.
45, 95% CI: 0.
36-0.
55) and the best ORR (OR: 0.
23, 95% CI: 0.
12-0.
42) .
Subgroup analysis showed that for patients with PD-L1<1%, nivolumab + ipilimumab + chemotherapy is associated with the best OS; for patients with PD-L1 ≥ 1%, pembrolizumab + Chemotherapy is associated with optimal OS.
In terms of safety, compared with other immunotherapy drugs combined with chemotherapy, pembrolizumab and sintilizumab have relatively fewer grade ≥3 adverse events.
The researchers pointed out that compared with the anti-PD-L1 combination regimen, the anti-PD-1 combination regimen may have a better survival outcome, and the safety of the two is equivalent.
Pembrolizumab + chemotherapy, nivolumab + ipilimumab + chemotherapy seem to be the best first-line immune combination for patients with PD-L1 positive and negative advanced NSCLC, respectively.
Although atilizumab + bevacizumab + chemotherapy can provide the best PFS and ORR, the simultaneous immunotherapy and chemotherapy can also increase toxicity, especially when anti-angiogenic drugs are added at the same time.
04 The Phase III CheckMate-648 clinical study of "O-drug" combination therapy for esophageal squamous cell carcinoma achieved positive results.
The global phase III CheckMate-648 study plan included 939 patients with esophageal squamous cell carcinoma, aiming to evaluate nivolumab + ipilim The difference in efficacy and safety of monoclonal antibody, nivolumab + chemotherapy, and chemotherapy as first-line therapy for patients with esophageal squamous cell carcinoma, 23 hospitals in China participated in the study.
Recently, BMS announced that the Phase III clinical study of CheckMate-648 has achieved positive results.
The results of the interim analysis showed that compared with chemotherapy, nivolumab + chemotherapy treatment resulted in statistically and clinically significant improvements in the OS and PFS of PD-L1 positive patients, reaching two primary endpoints.
At the same time, the OS of all the intent-to-treat (ITT) populations also had significant statistical and clinically significant improvements, reaching secondary endpoints.
Nivolumab + ipilimumab also had significant statistical and clinically significant improvements in the OS of PD-L1 positive patients and ITT (intent-to-treat population) patients, reaching primary and secondary endpoints.
However, nivolumab + ipilimumab failed to prolong the PFS, another primary endpoint, in PD-L1 positive patients.
05 KEYNOTE-564 Phase III study of "K drug" adjuvant therapy for renal cell carcinoma was successful KEYNOTE-564 study is a randomized, double-blind, phase III clinical trial to evaluate the role of "K drug" pembrolizumab Monotherapy is the adjuvant treatment of renal cell carcinoma (RCC) patients with medium to high risk, high risk or M1 NED after nephrectomy.
A total of 950 patients were recruited in the study, and they were randomized to receive Keytruda (200 mg intravenously on the first day of each cycle, 1 cycle every 3 weeks, up to 17 cycles of treatment) or placebo treatment.
The primary endpoint is disease-free survival (DFS), and the secondary endpoints include OS and safety results.
Recently, Merck announced that the phase III clinical study of KEYNOTE-564 has reached the primary endpoint.
According to an interim analysis conducted by the Independent Data Monitoring Committee, patients receiving pembrolizumab monotherapy had statistically significant and clinically significant improvements in disease-free survival (DFS) compared with placebo.
The study will continue to evaluate whether pembrolizumab can reach the key secondary endpoint of prolonging the patient's OS.
It is worth noting that the success of the KEYNOTE-564 study will make Pembrolizumab the first PD-1 monoclonal antibody that has shown positive results in adjuvant treatment of renal cell carcinoma.
06 New drug: First-line NSCLC, Ametinib is planned to be included in breakthrough therapy Recently, the official website of the National Medical Products Administration (NMPA) showed that Hausen Pharmaceuticals' third-generation EGFR inhibitor, Ametinib, is planned to be included in breakthrough therapy for first-line use Treatment of EGFR mutation-positive locally advanced or metastatic NSCLC.
Related information on the NMPA official website is reported that Ametinib has achieved positive results in the first-line treatment of EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) in the Phase III study, reaching the preset primary research endpoint.
Prior to this, Ametinib has been approved in China for the second-line treatment of NSCLC patients with treated EGFR T790M mutation.
References: [1]Li D,Chi Y,Chen X,et al.
Anlotinib in Locally Advanced or Metastatic Medullary Thyroid Carcinoma:A Randomized,Double-Blind Phase IIB Trial[J].
Clin Cancer Res.
Published:April 8, 2021.
DOI:10.
1158/1078-0432.
CCR-20-2950[2]Palmbos PL.
,Daignault-Newton S,Tomlins SA,et al.
A Randomized Phase II Study of Androgen Deprivation Therapy with or without Palbociclib in RB-positive Metastatic Hormone-Sensitive Prostate Cancer[J].
Clin Cancer Res.
Published:April 8,2021.
DOI:10.
1158/1078-0432.
CCR-21-0024[3]Liu L,Bai H,Wang C,et al.
Efficacy and Safety of First-Line Immunotherapy Combinations for Advanced Non-Small-Cell Lung Cancer:A Systematic Review and Network Meta-Analysis[J].
J Thorac Oncol.
Published:April 08,2021.
DOI:https://doi.
org /10.
1016/j.
jtho.
2021.
03.
016[4]https://mp.
weixin.
qq.
com/s/QHmN9pNZIC7pFaHcApdB-w[5]https://mp.
weixin.
qq.
com/s/0Gpc2fdJp5npGSqwcQGqbA[6]https://mp.
weixin.
qq.
com/s/Lqpc0styyTDGVukIpMWB6Q
CCR: Androgen deprivation therapy combined with piperacillil does not improve RB-positive metastasis Sex hormone-sensitive prostate cancer prognosis JTO: Anti-PD-1 monoclonal antibody combination regimen has better survival results in the first-line treatment of advanced non-small cell lung cancer.
"O drug" combination therapy for the treatment of esophageal squamous cell carcinoma Phase III clinical study CheckMate-648 achieved positive results" The successful Phase III study of KEYNOTE-564 in the single-agent adjuvant treatment of renal cell carcinoma of K drug: Ametinib is used in the first-line treatment of NSCLC to be included in the breakthrough therapy 01CCR: Anlotinib is safe in the treatment of locally advanced or metastatic medullary thyroid cancer Effective April 8, the ALTER 01031 study reported by Clinical Cancer Research showed that Anlotinib is safe and effective in the treatment of locally advanced or metastatic medullary thyroid carcinoma (MTC).
Screenshot of the cover of the article Anlotinib is a new type of multi-target tyrosine kinase inhibitor that can target the targets VEGFR, PDGFR, FGFR and c-Kit.
This randomized, double-blind, phase IIB study aims to evaluate the efficacy and safety of Anlotinib in the treatment of MTC.
The study included patients with unresectable locally advanced or metastatic MTC confirmed by histopathology and randomly assigned to receive anlotinib (12 mg, qd, d1-14, every 3 weeks as a treatment cycle) or comfort at a 2:1 ratio Drug treatment; patients in the placebo group are allowed to receive open-label anlotinib treatment after the disease has progressed.
The primary endpoint is progression-free survival (PFS).
Secondary endpoints include objective response rate (ORR), disease control rate (DCR), and overall survival (OS).
The results showed that a total of 91 patients were enrolled.
The median PFS of the anlotinib group was significantly longer than that of the placebo group (20.
7 months vs 11.
1 months, HR 0.
53, P=0.
029).
The ORR of anlotinib treatment reached 48.
4%.
The incidence of treatment-related adverse events (TRAE) in the anlotinib group and placebo group was 100% and 89.
7%, respectively.
The most common TRAEs (all grades) in the Anlotinib group included palmoplantar sensory loss erythema syndrome (62.
9%), proteinuria (61.
3%), and hypertriglyceridemia (48.
4%).
The researchers pointed out that MTC accounts for about 2% of all thyroid cancers, and its prognosis is relatively poor compared with differentiated thyroid cancers.
In this phase IIB study, Anlotinib has shown good efficacy and safety in the treatment of MTC, and may become a new treatment option for this rare disease, especially for Chinese patients.
02CCR: Androgen deprivation treatment combined with piperacillide does not improve the prognosis of RB-positive metastatic hormone-sensitive prostate cancer.
On April 8, a randomized phase II study reported by Clinical Cancer Research showed that compared with androgen deprivation (AD) treatment, Pipercillil+AD treatment did not improve the prognosis of retinoblastoma gene (RB)-positive metastatic hormone-sensitive prostate cancer (mHSPC).
Screenshot of the cover of the article.
Piperacillil is a cyclin-dependent kinase (CDK) 4/6 inhibitor.
Preclinical prostate cancer model studies have shown that CDK4/6 can bind to cyclin D (cyclin D), activate RB to release the transcription factor E2F, promote the transcription of cell cycle-related genes, and make the cell enter the S phase.
CDK4/6i can effectively block the progression of tumor cells from G1 phase to S phase.
The study hypothesized that the combined targeting of the androgen receptor and cyclin would improve the prognosis of mHSPC patients.
The study included 60 RB-positive mHSPC patients who were randomly (1:2) divided into group 1 (AD) or group 2 (AD + piperacillil).
The primary endpoint is the prostate-specific antigen (PSA) remission rate (RR) after 28 weeks of treatment.
Secondary endpoints include safety, PSA level and clinical PFS and radiological RR.
Count circulating tumor cells (CTC) at various time points, and perform exome sequencing of tumors when feasible.
The results showed that a total of 72 mHSPC patients underwent metastatic disease biopsy.
64 patients had enough tissue for RB evaluation, of which 62 (97%) still had RB expression.
A total of 60 patients received treatment (group 1: 20 cases; group 2: 40 cases).
At 28 weeks, 80% of patients (group 1: 16/20, group 2: 32/40; P=0.
87) reached the primary PSA endpoint ≤ 4ng/mL, and the undetectable rates of PSA in group 1 and group 2 were respectively 50% and 43% (P=0.
5).
The radiological RR of group 1 and group 2 were both 89%, and the 12-month PSA-PFS rate (PSA progression-free survival) was 69% and 74%, respectively (P=0.
72).
Mutations in TP53 and PIK3 pathways, 8q copy number gain, and CTC before treatment are associated with decreased PSA-PFS.
In terms of safety, the most common grade 3/4 adverse event in Group 2 was neutropenia.
The researchers said that piperacillil failed to affect the prognosis of RB-positive mHSPC.
03JTO: The anti-PD-1 monoclonal antibody combination regimen has better survival results in the first-line treatment of advanced non-small cell lung cancer.
On April 8, a systematic review and network meta-analysis reported in the Journal of Thoracic Oncology showed that in advanced non-small cell lung cancer ( In the first-line immune combination therapy of NSCLC, the anti-programmed death molecule 1 (PD-1) combination program may have better survival results and comparable safety than the anti-programmed death ligand 1 (PD-L1) combination program Sex.
Screenshot of the cover of the article.
Although a series of randomized controlled trials on the first-line immune combination therapy for advanced NSCLC have studied different combinations, the best combination strategy has yet to be determined. To this end, the researchers searched PubMed, Embase, Cochrane library, ClinicalTrials.
gov, and related literature from large international conferences to conduct systematic reviews and Bayesian network meta-analysis to compare immunocombination therapy with other therapies for first-line treatment of patients with advanced NSCLC.
effect.
The results showed that a total of 16 studies were analyzed, involving 8,278 patients and 10 immunization combinations.
Pembrolizumab + chemotherapy, sintilizumab + chemotherapy can provide the best OS benefit (HR: 0.
96, 95% CI: 0.
72-1.
29).
Atelizumab + bevacizumab + chemotherapy seems to provide the best PFS (HR: 0.
45, 95% CI: 0.
36-0.
55) and the best ORR (OR: 0.
23, 95% CI: 0.
12-0.
42) .
Subgroup analysis showed that for patients with PD-L1<1%, nivolumab + ipilimumab + chemotherapy is associated with the best OS; for patients with PD-L1 ≥ 1%, pembrolizumab + Chemotherapy is associated with optimal OS.
In terms of safety, compared with other immunotherapy drugs combined with chemotherapy, pembrolizumab and sintilizumab have relatively fewer grade ≥3 adverse events.
The researchers pointed out that compared with the anti-PD-L1 combination regimen, the anti-PD-1 combination regimen may have a better survival outcome, and the safety of the two is equivalent.
Pembrolizumab + chemotherapy, nivolumab + ipilimumab + chemotherapy seem to be the best first-line immune combination for patients with PD-L1 positive and negative advanced NSCLC, respectively.
Although atilizumab + bevacizumab + chemotherapy can provide the best PFS and ORR, the simultaneous immunotherapy and chemotherapy can also increase toxicity, especially when anti-angiogenic drugs are added at the same time.
04 The Phase III CheckMate-648 clinical study of "O-drug" combination therapy for esophageal squamous cell carcinoma achieved positive results.
The global phase III CheckMate-648 study plan included 939 patients with esophageal squamous cell carcinoma, aiming to evaluate nivolumab + ipilim The difference in efficacy and safety of monoclonal antibody, nivolumab + chemotherapy, and chemotherapy as first-line therapy for patients with esophageal squamous cell carcinoma, 23 hospitals in China participated in the study.
Recently, BMS announced that the Phase III clinical study of CheckMate-648 has achieved positive results.
The results of the interim analysis showed that compared with chemotherapy, nivolumab + chemotherapy treatment resulted in statistically and clinically significant improvements in the OS and PFS of PD-L1 positive patients, reaching two primary endpoints.
At the same time, the OS of all the intent-to-treat (ITT) populations also had significant statistical and clinically significant improvements, reaching secondary endpoints.
Nivolumab + ipilimumab also had significant statistical and clinically significant improvements in the OS of PD-L1 positive patients and ITT (intent-to-treat population) patients, reaching primary and secondary endpoints.
However, nivolumab + ipilimumab failed to prolong the PFS, another primary endpoint, in PD-L1 positive patients.
05 KEYNOTE-564 Phase III study of "K drug" adjuvant therapy for renal cell carcinoma was successful KEYNOTE-564 study is a randomized, double-blind, phase III clinical trial to evaluate the role of "K drug" pembrolizumab Monotherapy is the adjuvant treatment of renal cell carcinoma (RCC) patients with medium to high risk, high risk or M1 NED after nephrectomy.
A total of 950 patients were recruited in the study, and they were randomized to receive Keytruda (200 mg intravenously on the first day of each cycle, 1 cycle every 3 weeks, up to 17 cycles of treatment) or placebo treatment.
The primary endpoint is disease-free survival (DFS), and the secondary endpoints include OS and safety results.
Recently, Merck announced that the phase III clinical study of KEYNOTE-564 has reached the primary endpoint.
According to an interim analysis conducted by the Independent Data Monitoring Committee, patients receiving pembrolizumab monotherapy had statistically significant and clinically significant improvements in disease-free survival (DFS) compared with placebo.
The study will continue to evaluate whether pembrolizumab can reach the key secondary endpoint of prolonging the patient's OS.
It is worth noting that the success of the KEYNOTE-564 study will make Pembrolizumab the first PD-1 monoclonal antibody that has shown positive results in adjuvant treatment of renal cell carcinoma.
06 New drug: First-line NSCLC, Ametinib is planned to be included in breakthrough therapy Recently, the official website of the National Medical Products Administration (NMPA) showed that Hausen Pharmaceuticals' third-generation EGFR inhibitor, Ametinib, is planned to be included in breakthrough therapy for first-line use Treatment of EGFR mutation-positive locally advanced or metastatic NSCLC.
Related information on the NMPA official website is reported that Ametinib has achieved positive results in the first-line treatment of EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) in the Phase III study, reaching the preset primary research endpoint.
Prior to this, Ametinib has been approved in China for the second-line treatment of NSCLC patients with treated EGFR T790M mutation.
References: [1]Li D,Chi Y,Chen X,et al.
Anlotinib in Locally Advanced or Metastatic Medullary Thyroid Carcinoma:A Randomized,Double-Blind Phase IIB Trial[J].
Clin Cancer Res.
Published:April 8, 2021.
DOI:10.
1158/1078-0432.
CCR-20-2950[2]Palmbos PL.
,Daignault-Newton S,Tomlins SA,et al.
A Randomized Phase II Study of Androgen Deprivation Therapy with or without Palbociclib in RB-positive Metastatic Hormone-Sensitive Prostate Cancer[J].
Clin Cancer Res.
Published:April 8,2021.
DOI:10.
1158/1078-0432.
CCR-21-0024[3]Liu L,Bai H,Wang C,et al.
Efficacy and Safety of First-Line Immunotherapy Combinations for Advanced Non-Small-Cell Lung Cancer:A Systematic Review and Network Meta-Analysis[J].
J Thorac Oncol.
Published:April 08,2021.
DOI:https://doi.
org /10.
1016/j.
jtho.
2021.
03.
016[4]https://mp.
weixin.
qq.
com/s/QHmN9pNZIC7pFaHcApdB-w[5]https://mp.
weixin.
qq.
com/s/0Gpc2fdJp5npGSqwcQGqbA[6]https://mp.
weixin.
qq.
com/s/Lqpc0styyTDGVukIpMWB6Q
