-
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
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
On April 17th (this Saturday), China's original third-generation EGFR-TKI targeted drug vometinib mesylate (Ivesa®) was used for EGFR mutation-positive stage II-IIIA non-small cell lung cancer ( The clinical study (FORWARD) of postoperative adjuvant treatment for patients with NSCLC will be officially launched.
The study plan enrolled 318 patients (Chinese population) with EGFR mutation-positive stage II-IIIA NSCLC patients who underwent radical resection with or without adjuvant chemotherapy, and were randomly assigned to receive vometinib (80 mg/day/time) or Placebo treatment until disease recurrence, termination of treatment or completion of treatment; the primary endpoint of the study is disease-free survival (DFS).
International Standard China Speed On March 26 this year, "The Lancet Respiratory Medicine" (The Lancet Respiratory Medicine, impact factor 25.
094) published the full online phase IIb clinical study of vometinib in the treatment of patients with EGFR T790M mutation in advanced NSCLC (NCT03452592) Results: Among 220 subjects enrolled in the Phase IIb study, the objective response rate (ORR) of 80 mg vomitinib reached 74%, the disease control rate (DCR) reached 94%, and the median progression-free survival The period (PFS) is 9.
6 months, and the median overall survival time (OS) has not yet been reached.
Among subjects with central nervous system (CNS) metastasis, the CNS ORR reached 66%, the CNS DCR reached 100%, and the median CNS PFS was 11.
6 months1.
On March 3 this year, vometinib mesylate (hereinafter referred to as vometinib) was approved by the National Medical Products Administration of my country for the treatment of disease progression during or after treatment with EGFR-TKI, and Testing confirmed the presence of EGFR T790M mutation-positive adult patients with locally advanced or metastatic NSCLC.
The FORWARD study follows the global Phase III registered clinical study ADAURA released in 2020, and is another to explore the third generation of EGFR-TKI (epidermal growth factor receptor-tyrosine kinase inhibitor) drugs as adjuvant therapy for EGFR Mutation (exon 19 deletion or exon 21L858R substitution mutation), complete resection (R0 resection) in stage II-IIIA NSCLC patients with the efficacy and safety of the key registration phase III clinical study.
Unlike the ADAURA study, the FORWARD study only included Chinese patients.
Postoperative assistance is the trend of the "three generations", the wave behind the wave before the wave, ADAURA research is undoubtedly the most breakthrough clinical research in the field of lung cancer treatment in 2020.
The ADAURA study is a global phase III, double-blind, randomized controlled clinical study.
The results were first reported at the 2020 American Society of Clinical Oncology (ASCO) conference and subsequently published in the New England Journal of Medicine.
The results of the study showed that compared with the placebo group, the third-generation EGFR-TKI significantly prolonged the median DFS of patients with stage II-IIIA (less than 19.
6 months, P<0.
001), and reduced disease recurrence or death by 83% Risk (HR=0.
17,99% CI=0.
11-0.
26) 2.
The ADAURA study reached the main research endpoint: it reduced the risk of disease recurrence or death by 83%.
2 Another clinical study of EGFR-TKI for the adjuvant treatment of early NSCLC in the Chinese patient population is also attracting attention.
At the 21st World Lung Cancer Conference held in January this year, the first-generation EGFR-TKI targeted drug icotinib originally developed in China was used in the postoperative adjuvant treatment of stage II-IIIA operable Chinese NSCLC population.
Random and open Label Phase III clinical study (EVIDENCE) results announced 3: The median DFS of the first-generation EGFR-TKI reached 46.
95 months, which was significantly better than the control group (adjuvant chemotherapy) at 22.
11 months (HR=0.
36, p<0.
0001), disease The risk of recurrence is reduced by 64%3. The EVIDENCE study reached the main research endpoint: it reduced the risk of disease recurrence or death by 64%.
3 The third-generation EGFR-TKI has global, randomized, double-blind Phase III clinical study (FLAURA) data results, which proves that it is compared to the first Substitution of EGFR-TKI (erlotinib/gefitinib) in the treatment of stage IV NSCLC can bring more significant overall survival (OS) benefits, with a median OS extension of 6.
7 months and a 20% reduction in the risk of death4.
The results of this study have rewritten the guidelines for diagnosis and treatment of lung cancer in various countries and become the first-line standard treatment for advanced EGFR mutation-positive (19Del/21 L858R) NSCLC.
FLAURA study: The third-generation EGFR-TKI osimertinib brings significant OS benefits compared with the first-generation EGFR-TKI 4 Effective control of brain metastases, lung cancer cure or long-term survival The third-generation EGFR-TKI first-line treatment of advanced NSCLC shows The advantage of OS stems from the difference between its biochemical mechanism of action and the first-generation EGFR-TKI.
The third-generation EGFR-TKI irreversibly binds to sensitive mutations (19Del/21 L858R) and T790M mutation EGFR, so the inhibition time of EGFR can be longer; and the third-generation EGFR-TKI can penetrate the blood-brain barrier, so it is useful for concomitant brain metastases The NSCLC population showed a higher objective tumor response rate (ORR).
At the World Lung Cancer Conference held in January this year, the results of the Phase I-II Dose Expansion Study (NCT03127449) of the CNS metastatic population of vometinib in the treatment of EGFR T790M mutation-positive locally advanced or metastatic NSCLC showed that 80 mg vometinib The CNS objective response rate (ORR) of 160 mg vomitinib reached 60.
0%, and the CNS ORR of 160 mg vomitinib reached 84.
6%, and the CNS disease control rate (DCR) was 100%.
The curative effect has clinical significance5. WCLC announced the efficacy results for patients with CNS metastases in different dose groups (data deadline: 2020-01-29) Abbreviations: CNS, central nervous system; cEFR, CNS assessable efficacy set; cFAS, CNS complete analysis set; ORR, objective response rate ; DCR, disease control rate; PFS, progression-free survival; NR, failure to reach lung cancer brain metastasis is a common and serious clinical condition, and it is also one of the common reasons for the failure of lung cancer treatment.
In NSCLC, which accounts for 85% of all lung cancers, the incidence of brain metastases in patients with advanced NSCLC is 40%-50%, which is higher than other malignant tumors, and the median survival time is shorter6.
A retrospective study of 1672 patients with advanced lung cancer in China showed that among the first diagnosed NSCLC patients, 1/4 patients had brain metastases at the first diagnosis, and about 30%-48% of them would have brain metastases during treatment.
, And the first-generation EGFR-TKI patients have a significantly higher probability of brain metastasis than chemotherapy7.
The efficacy of the third-generation EGFR-TKI for CNS metastasis to NSCLC may also play a key role in reducing postoperative recurrence in early patients.
In the ADAURA study, the third-generation EGFR-TKI adjuvant treatment group had a reduction in the risk of central nervous system-related recurrence or death by 82%2.
ADAURA study: The third-generation EGFR-TKI reduces the risk of central nervous system-related recurrence or death by 82%.
2 Professor Wu Yilong, the life director of Guangdong People’s Hospital who led the ADAURA study, once pointed out that there are three dimensions to evaluate targeted therapy drugs for advanced lung cancer: One dimension is progression-free survival (PFS), that is, the effect of drugs to effectively control disease progression, the second is the safety of drugs, and the third dimension is the effect of controlling or even preventing brain metastases from lung cancer.
For long-term survival of lung cancer, the third dimension may be the most important one.
Although the third-generation EGFR-TKI treatment of early and late EGFR-sensitive mutant NSCLC has high-level evidence-based medical evidence, most of the evidence comes from global multi-center clinical studies for Asian and Chinese patients, as well as the treatment of EGFR L858R mutant NSCLC There are still some controversies about the efficacy.
FLAURA study subgroup OS analysis 4 In addition to the clinical studies on Chinese NSCLC patients such as FORWARD and EVIDENCE, a number of phase III registered clinical studies of the first-line treatment of advanced NSCLC with EGFR-sensitive mutations of the third-generation EGFR-TKI in China have also been registered in China.
Unfold.
It is believed that the data results of the efficacy and safety of the third-generation EGFR-TKI in the treatment of early and advanced NSCLC in China will be born in the near future.
References: 1.
Yuankai Shi, Xingsheng Hu, Shucai Zhang, et al.
Efficacy, safety, and genetic analysis of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small-cell lung cancer: a phase Ⅱb, multicentre, single -arm, open-label study.
Lancet Respir Med.
Published on March 26, 2021.
DOI: https://doi.
org/10.
1016/S2213-2600(20)30455-0.
2.
Yilong Wu, et al.
, Osimertinib in Resected EGFR-Mutated Non–Small-Cell Lung Cancer, N Engl J Med 2020; 383:1711-1723.
3.
Zhou C, et al.
Icotinib versus chemotherapy as adjuvant treatment for stage II–IIIA EGFR-mutant NSCLC (EVIDENCE): a randomized, open-label, phase 3 study.
WCLC2020.
4.
Ramalingam SS, Vansteenkiste J, Planchard D, et al.
Overall survival with osimertinib in untreated, EGFR-mutatedadvanced NSCLC.
N Engl J Med 2020; 382:41-50.
5.
Y.
Shi et al.
,CNS Efficacyof AST2818 in Patients with T790M-Positive Advanced NSCLC: Data from a PhaseI-II Dose-Expansion Study, 2020 WCLC, Abstract 3286.
6.
Peters S, et al.
The impact of brain metastasis on quality of life,resource utilizationand survival in patients withnon-small-cell lung cancer, Cancer Treatment Reviews.
2016;45:139 162.
7.
Wang BX et al.
, Impacts of EGFR mutation and EGFR-TKIs on incidence of brain metastases in advanced non-squamous NSCLC; Clinical Neurology and Neurosurgery 160 ( 2017) 96-100.
Impacts of EGFR mutation and EGFR-TKIs on incidence of brain metastases in advanced non-squamous NSCLC; Clinical Neurology and Neurosurgery 160 (2017) 96-100.
Impacts of EGFR mutation and EGFR-TKIs on incidence of brain metastases in advanced non-squamous NSCLC; Clinical Neurology and Neurosurgery 160 (2017) 96-100.
The study plan enrolled 318 patients (Chinese population) with EGFR mutation-positive stage II-IIIA NSCLC patients who underwent radical resection with or without adjuvant chemotherapy, and were randomly assigned to receive vometinib (80 mg/day/time) or Placebo treatment until disease recurrence, termination of treatment or completion of treatment; the primary endpoint of the study is disease-free survival (DFS).
International Standard China Speed On March 26 this year, "The Lancet Respiratory Medicine" (The Lancet Respiratory Medicine, impact factor 25.
094) published the full online phase IIb clinical study of vometinib in the treatment of patients with EGFR T790M mutation in advanced NSCLC (NCT03452592) Results: Among 220 subjects enrolled in the Phase IIb study, the objective response rate (ORR) of 80 mg vomitinib reached 74%, the disease control rate (DCR) reached 94%, and the median progression-free survival The period (PFS) is 9.
6 months, and the median overall survival time (OS) has not yet been reached.
Among subjects with central nervous system (CNS) metastasis, the CNS ORR reached 66%, the CNS DCR reached 100%, and the median CNS PFS was 11.
6 months1.
On March 3 this year, vometinib mesylate (hereinafter referred to as vometinib) was approved by the National Medical Products Administration of my country for the treatment of disease progression during or after treatment with EGFR-TKI, and Testing confirmed the presence of EGFR T790M mutation-positive adult patients with locally advanced or metastatic NSCLC.
The FORWARD study follows the global Phase III registered clinical study ADAURA released in 2020, and is another to explore the third generation of EGFR-TKI (epidermal growth factor receptor-tyrosine kinase inhibitor) drugs as adjuvant therapy for EGFR Mutation (exon 19 deletion or exon 21L858R substitution mutation), complete resection (R0 resection) in stage II-IIIA NSCLC patients with the efficacy and safety of the key registration phase III clinical study.
Unlike the ADAURA study, the FORWARD study only included Chinese patients.
Postoperative assistance is the trend of the "three generations", the wave behind the wave before the wave, ADAURA research is undoubtedly the most breakthrough clinical research in the field of lung cancer treatment in 2020.
The ADAURA study is a global phase III, double-blind, randomized controlled clinical study.
The results were first reported at the 2020 American Society of Clinical Oncology (ASCO) conference and subsequently published in the New England Journal of Medicine.
The results of the study showed that compared with the placebo group, the third-generation EGFR-TKI significantly prolonged the median DFS of patients with stage II-IIIA (less than 19.
6 months, P<0.
001), and reduced disease recurrence or death by 83% Risk (HR=0.
17,99% CI=0.
11-0.
26) 2.
The ADAURA study reached the main research endpoint: it reduced the risk of disease recurrence or death by 83%.
2 Another clinical study of EGFR-TKI for the adjuvant treatment of early NSCLC in the Chinese patient population is also attracting attention.
At the 21st World Lung Cancer Conference held in January this year, the first-generation EGFR-TKI targeted drug icotinib originally developed in China was used in the postoperative adjuvant treatment of stage II-IIIA operable Chinese NSCLC population.
Random and open Label Phase III clinical study (EVIDENCE) results announced 3: The median DFS of the first-generation EGFR-TKI reached 46.
95 months, which was significantly better than the control group (adjuvant chemotherapy) at 22.
11 months (HR=0.
36, p<0.
0001), disease The risk of recurrence is reduced by 64%3. The EVIDENCE study reached the main research endpoint: it reduced the risk of disease recurrence or death by 64%.
3 The third-generation EGFR-TKI has global, randomized, double-blind Phase III clinical study (FLAURA) data results, which proves that it is compared to the first Substitution of EGFR-TKI (erlotinib/gefitinib) in the treatment of stage IV NSCLC can bring more significant overall survival (OS) benefits, with a median OS extension of 6.
7 months and a 20% reduction in the risk of death4.
The results of this study have rewritten the guidelines for diagnosis and treatment of lung cancer in various countries and become the first-line standard treatment for advanced EGFR mutation-positive (19Del/21 L858R) NSCLC.
FLAURA study: The third-generation EGFR-TKI osimertinib brings significant OS benefits compared with the first-generation EGFR-TKI 4 Effective control of brain metastases, lung cancer cure or long-term survival The third-generation EGFR-TKI first-line treatment of advanced NSCLC shows The advantage of OS stems from the difference between its biochemical mechanism of action and the first-generation EGFR-TKI.
The third-generation EGFR-TKI irreversibly binds to sensitive mutations (19Del/21 L858R) and T790M mutation EGFR, so the inhibition time of EGFR can be longer; and the third-generation EGFR-TKI can penetrate the blood-brain barrier, so it is useful for concomitant brain metastases The NSCLC population showed a higher objective tumor response rate (ORR).
At the World Lung Cancer Conference held in January this year, the results of the Phase I-II Dose Expansion Study (NCT03127449) of the CNS metastatic population of vometinib in the treatment of EGFR T790M mutation-positive locally advanced or metastatic NSCLC showed that 80 mg vometinib The CNS objective response rate (ORR) of 160 mg vomitinib reached 60.
0%, and the CNS ORR of 160 mg vomitinib reached 84.
6%, and the CNS disease control rate (DCR) was 100%.
The curative effect has clinical significance5. WCLC announced the efficacy results for patients with CNS metastases in different dose groups (data deadline: 2020-01-29) Abbreviations: CNS, central nervous system; cEFR, CNS assessable efficacy set; cFAS, CNS complete analysis set; ORR, objective response rate ; DCR, disease control rate; PFS, progression-free survival; NR, failure to reach lung cancer brain metastasis is a common and serious clinical condition, and it is also one of the common reasons for the failure of lung cancer treatment.
In NSCLC, which accounts for 85% of all lung cancers, the incidence of brain metastases in patients with advanced NSCLC is 40%-50%, which is higher than other malignant tumors, and the median survival time is shorter6.
A retrospective study of 1672 patients with advanced lung cancer in China showed that among the first diagnosed NSCLC patients, 1/4 patients had brain metastases at the first diagnosis, and about 30%-48% of them would have brain metastases during treatment.
, And the first-generation EGFR-TKI patients have a significantly higher probability of brain metastasis than chemotherapy7.
The efficacy of the third-generation EGFR-TKI for CNS metastasis to NSCLC may also play a key role in reducing postoperative recurrence in early patients.
In the ADAURA study, the third-generation EGFR-TKI adjuvant treatment group had a reduction in the risk of central nervous system-related recurrence or death by 82%2.
ADAURA study: The third-generation EGFR-TKI reduces the risk of central nervous system-related recurrence or death by 82%.
2 Professor Wu Yilong, the life director of Guangdong People’s Hospital who led the ADAURA study, once pointed out that there are three dimensions to evaluate targeted therapy drugs for advanced lung cancer: One dimension is progression-free survival (PFS), that is, the effect of drugs to effectively control disease progression, the second is the safety of drugs, and the third dimension is the effect of controlling or even preventing brain metastases from lung cancer.
For long-term survival of lung cancer, the third dimension may be the most important one.
Although the third-generation EGFR-TKI treatment of early and late EGFR-sensitive mutant NSCLC has high-level evidence-based medical evidence, most of the evidence comes from global multi-center clinical studies for Asian and Chinese patients, as well as the treatment of EGFR L858R mutant NSCLC There are still some controversies about the efficacy.
FLAURA study subgroup OS analysis 4 In addition to the clinical studies on Chinese NSCLC patients such as FORWARD and EVIDENCE, a number of phase III registered clinical studies of the first-line treatment of advanced NSCLC with EGFR-sensitive mutations of the third-generation EGFR-TKI in China have also been registered in China.
Unfold.
It is believed that the data results of the efficacy and safety of the third-generation EGFR-TKI in the treatment of early and advanced NSCLC in China will be born in the near future.
References: 1.
Yuankai Shi, Xingsheng Hu, Shucai Zhang, et al.
Efficacy, safety, and genetic analysis of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small-cell lung cancer: a phase Ⅱb, multicentre, single -arm, open-label study.
Lancet Respir Med.
Published on March 26, 2021.
DOI: https://doi.
org/10.
1016/S2213-2600(20)30455-0.
2.
Yilong Wu, et al.
, Osimertinib in Resected EGFR-Mutated Non–Small-Cell Lung Cancer, N Engl J Med 2020; 383:1711-1723.
3.
Zhou C, et al.
Icotinib versus chemotherapy as adjuvant treatment for stage II–IIIA EGFR-mutant NSCLC (EVIDENCE): a randomized, open-label, phase 3 study.
WCLC2020.
4.
Ramalingam SS, Vansteenkiste J, Planchard D, et al.
Overall survival with osimertinib in untreated, EGFR-mutatedadvanced NSCLC.
N Engl J Med 2020; 382:41-50.
5.
Y.
Shi et al.
,CNS Efficacyof AST2818 in Patients with T790M-Positive Advanced NSCLC: Data from a PhaseI-II Dose-Expansion Study, 2020 WCLC, Abstract 3286.
6.
Peters S, et al.
The impact of brain metastasis on quality of life,resource utilizationand survival in patients withnon-small-cell lung cancer, Cancer Treatment Reviews.
2016;45:139 162.
7.
Wang BX et al.
, Impacts of EGFR mutation and EGFR-TKIs on incidence of brain metastases in advanced non-squamous NSCLC; Clinical Neurology and Neurosurgery 160 ( 2017) 96-100.
Impacts of EGFR mutation and EGFR-TKIs on incidence of brain metastases in advanced non-squamous NSCLC; Clinical Neurology and Neurosurgery 160 (2017) 96-100.
Impacts of EGFR mutation and EGFR-TKIs on incidence of brain metastases in advanced non-squamous NSCLC; Clinical Neurology and Neurosurgery 160 (2017) 96-100.
