-
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
Article source: Med
Author: Xixi
Medical journals, in addition to the legendary CA, the four out-of-reach journals NEJM, Lancet, JAMA, BMJ, and the CNS that can be met but not sought, the unique Cancer Cell must have a name
Cancer Cell (IF: 31.
Recently, a multicenter phase 3 study of bevacizumab (A) combined with erlotinib (T) in the first-line treatment of EGFR-mutant advanced non-small cell carcinoma (NSCLC) was officially published in Cancer Cell
The day after the research was published, Professor Wu Yilong expressed his thoughts in the circle of friends: "It took 6 years from design, implementation to publication.
What is Raider?
Specifically, in addition to confirming the known PFS benefits of VEGF/EGFR targeted therapy, the CTONG1509 study also showed that patients with exon 21 mutations and brain metastases may obtain special benefits
Figure: ARTEMIS-CTONG1509 research chart summary
Today’s article, let’s talk about it~~
First of all, what does it mean that patients with L858R mutation in exon 21 benefit more?
First of all, what does it mean that patients with L858R mutation in exon 21 benefit more?Due to different biological characteristics, clinical characteristics, and sensitivity to TKI, exon 19 deletion (19Del) and exon 21 mutation (L858R) have traditionally been regarded as "two different diseases
The common sense in the past is that patients with L858R mutations have a worse response to EGFR-TKI than patients with 19Del mutations
However, in the ARTEMIS study, the median PFS improvement of the L858R population (+9.
Figure: PFS curve stratified according to the baseline EGFR mutation type in the CTONG1509 study
As the saying goes: "For the 21 mutations with poor single-drug effect, the advantage of combined therapy actually exceeds the consistently good 19 deletions.
Knowledge Card: At present, a large number of RCTs and meta-analysis have confirmed that different TKIs have different efficacy in different EGFR mutation subtypes, and support different mutations for treatment subdivision
Secondly, why is the brain metastasis subgroup data particularly worthy of attention?
Secondly, why is the brain metastasis subgroup data particularly worthy of attention?The incidence of brain metastases in EGFR-mutant NSCLC patients is as high as 40%, especially for sensitive mutations.
Compared with traditional chemotherapy, TKI drugs have achieved exciting effects in brain metastases due to their small molecular weight, advantages in lipid-water ratio, and good permeability, and have greatly promoted the treatment of EGFR-sensitive mutant brain metastases
However, due to concerns about potential bleeding risks, most previous studies (such as RELAY) did not enroll patients with central nervous system (CNS) metastasis
In the ARTEMIS study, 91 patients with baseline asymptomatic CNS metastases were enrolled.
Figure: PFS curve stratified by baseline brain metastasis in the CTONG1509 study
The author pointed out in the discussion: "Compared with the FLAURA study and the FLAURA China study, the patients with brain metastases observed in the CTONG1509 study benefited more
Knowledge Card: In addition to the CTONG1509 study, previous PASSPORT, BRAIN and AVAIL studies have also confirmed the safety and efficacy of bevacizumab combined with chemotherapy or targeted therapy for NSCLC brain metastases
Finally, how to choose clinical first-line treatment?
Finally, how to choose clinical first-line treatment?Source: CSCO 2020
At present, for patients with different EGFR mutations, there are multiple first-generation TKIs, second-generation TKI afatinib and dacomitinib, third-generation osimertinib, and TKI combined with anti-angiogenesis therapy and combined chemotherapy
.
So, how should first-line treatment be selected? At the 17th China Lung Cancer Summit Forum in 2020, many oncologists from different disciplines reached the following consensus:
It is necessary to subdivide the two subtypes of EGFR sensitive mutations (exon19 and exon21 L858R) and whether they are accompanied by brain metastasis, and give different treatments:
For exon19 deletion, osimertinib or afatinib is preferred; for exon21 L858R mutation, dacomitinib, erlotinib+bevacizumab or icotinib are preferred; for patients with brain metastases, priority is given Recommend osimertinib and icotinib
.
To sum up, different TKIs have different efficacy in different EGFR mutation subtypes, so the treatment plan should be subdivided for EGFR subtypes, but prospective research data still needs to be verified
.
Although the type of EGFR mutation is the most important prognostic factor, it is necessary to consider whether it is accompanied by brain metastasis when choosing a treatment strategy
.
The response to these questions is perhaps one of the secrets of CTONG1509 research being favored by top journals!
Of course, there is no regret for not having a successful clinical study
.
Why is the OS of the CTONG1509 study both in the experimental group and the control group lower than the Japanese JO25567 study? Although the current OS data is still immature, why did the author say in the discussion that the A+T model is unlikely to extend the OS? What does this have to do with the resistance pattern behind it? This Phase 3 clinical trial published for the first time in the history of Cancer Cell has a lot to be tasted
.
Note: The original text has been deleted
Reference materials:
[1]Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study.
Cancer Cell.
2021 Jul 20:S1535-6108(21)00382-2.
[2] An interview with the 2020 China Lung Cancer Summit Forum