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"Dual-target combination" new indication approved in my country, "dabrafenib" combined with "trametinib" brings a new option for patients with BRAF V600 mutant non-small cell lung cancer

 Last Update: 2022-04-23
 Source: Internet
 Author: User

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On March 25 , 2022 , Novartis (China) dual-targeted combination therapy drugs Tefera® ( dabrafenib mesylate capsules) and Megenin® ( trametinib tablets) were approved by the State Drug Administration.
The agency approved an additional indication for the treatment of BRAF V600 mutation-positive metastatic non-small cell lung cancer .
This is not only the third approved indication of Tefero® and Megenin® , but also the first dual-targeted combination therapy drug approved in China for BRAF V600 mutation-positive metastatic non-small cell lung cancer .

The agency approved an additional indication for the treatment of BRAF V600 mutation-positive metastatic non-small cell lung cancer .
This is not only the third approved indication of Tefero® and Megenin® , but also the first dual-targeted combination therapy drug approved in China for BRAF V600 mutation-positive metastatic non-small cell lung cancer .

Previously, Teferox® and Megenin® have been approved for adjuvant therapy after complete resection of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma and BRAF V600 mutation-positive stage III melanoma
.

This also means that Chinese patients with rare mutations in lung cancer will bring new treatment options, which is another important milestone in the field of lung cancer targeted therapy

Ms.
Isabel Afonso , general manager of Novartis Oncology (China) , said: " Novartis always puts the health of patients first .
To meet diverse clinical needs, Novartis continues to introduce a variety of lung cancer drugs into China, including Many lung cancer patients, including rare targets, will bring more innovative therapies and solutions, and work with Chinese doctors to create health and well-being for patients .

BRAF V600 mutation, limited clinical benefit for patients BRAF V600 mutation, limited clinical benefit for patients

Lung cancer is the malignant tumor with the highest morbidity and mortality in China, of which non-small cell lung cancer ( NSCLC ) accounts for about 85% of lung cancer
.

In NSCLC , the BRAF gene mutation rate is 1.
5%-3.
5% ; BRAF V600 accounts for about 50% of all BRAF mutations , of which the most common type is V600E mutation .

Lung cancer is the malignant tumor with the highest morbidity and mortality in China, of which non-small cell lung cancer ( NSCLC ) accounts for about 85% of lung cancer

The BRAF driver gene is a key molecule in the mitogen-activated protein kinase ( MAPK ) pathway.
BRAF mutation can lead to the continuous activation of the downstream cell signal transduction pathway of MAPK , promote cell growth and proliferation, and mediate tumorigenesis .
According to the dependence on RAS kinase and the dimerization characteristics of RAF , BRAF mutations can be divided into classes I , II and III .
Among them, class I mutations are RAS kinase-independent monomers with high kinase activity, represented by BRAF V600 mutation; class II mutations are RAS kinase-independent dimers with kinase activity, such as G464 and G469 mutations; Class III mutations are RAS kinase-dependent, kinase-inactive heterodimers, including D594 and G466 mutations .

Currently, chemotherapy and immunotherapy targeting patients with BRAF V600 mutations have suboptimal clinical benefits, poor prognosis, and short overall survival

Crack the BRAF V600 mutation and open a new milestone in targeted therapy for NSCLC Crack the BRAF V600 mutation and open a new milestone in targeted therapy for NSCLC

In patients with BRAF V600E - mutated NSCLC , small-molecule targeted drugs have shown promising therapeutic prospects
.

Clinical studies have shown that the treatment regimen of BRAF inhibitor dabrafenib combined with MEK inhibitor trametinib can significantly prolong the survival of such patients with controllable safety

In patients with BRAF V600E - mutated NSCLC , small-molecule targeted drugs have shown promising therapeutic prospects

Dabrafenib combined with trametinib dual-target combination adopts an innovative mechanism of comprehensively inhibiting the upstream and downstream pathways of MAPK .
Dabrafenib is a selective inhibitor of BRAF kinase activity; trametinib is a reversible, highly selective allosteric inhibitor of MEK1 and MEK2 kinase activity, and the combination of the two can inhibit both BRAF and MEK simultaneously.
A target for rapid and significant remission of the lesions .

The global multicenter, open-label Phase II trial , CDRB436E2201 , demonstrated dabrafenib as monotherapy in previously treated patients (cohort A ), in combination with trametinib in previously treated patients (cohort B ), and in combination with trametinib Treatment-naïve patients (cohort C ) all had significant efficacy, with objective response rates ( ORR ) of 33.

0% , 63.
2% , and 64.

The approval of this indication in China is based on a registration clinical study of dabrafenib combined with trametinib in the treatment of BRAF mutation-positive metastatic NSCLC in the Chinese population .
The study is a national multi-center phase II clinical trial led by Professor Zhang Zhang from Sun Yat-sen University Cancer Center .
The study confirmed that dabrafenib combined with trametinib has excellent curative effect on BRAF V600E -mutated metastatic NSCLC .
The report of the recent international conference was released .

"The domestic approval of dabrafenib combined with trametinib for the treatment of BRAF - mutated lung cancer is an exciting thing, making BRAF V600 another targetable gene mutation for advanced NSCLC after EGFR , ALK , and ROS1 .
This is another important milestone in the field of targeted therapy for lung cancer .
” Professor Zhang Li, director of the Department of Oncology, Sun Yat-sen University Cancer Center, and chief expert on lung cancer, said, “BRAF V600 mutation is a rare driver gene for advanced NSCLC .
Poor prognosis .
Dabrafenib combined with trametinib in the China Lung Cancer Registry Study and the global CDRB436E2201 series showed that both dabrafenib combined with trametinib in the treatment of patients with BRAF V600 - mutant NSCLC , whether as first-line or later-line therapy Good efficacy, compared with single target, chemotherapy and immunotherapy, dabrafenib combined with trametinib shows efficacy advantages .
At the same time, compared with the global CDRB436E2201 study, combined with data analysis, it is found that Chinese lung cancer patients are more sensitive to dabrafenib combined with trametinib The efficacy of metinib is consistent with the global .
Dabrafenib combined with trametinib has shown significant efficacy in the adjuvant treatment of advanced melanoma and melanoma before. There is another effective treatment for mutant lung cancer, and it also opens a new direction for targeted therapy in adjuvant treatment of NSCLC patients .
In addition, the way of oral administration also makes patients more convenient and more compliant .
" This regimen has been recommended as a first-line treatment option for BRAF V600E/V600 - mutant NSCLC by multiple guidelines at home and abroad , including the National Comprehensive Cancer Network NCCN , the European Society for Medical Oncology ESMO , and the Chinese Society of Clinical Oncology CSCO .

Dr.
Wang Xingli, head of Novartis Global Drug Development (China), said: "' Patient-centric ' runs through Novartis' entire R&D process .
For this new indication of dabrafenib combined with trametinib , starting from the research design, We are working hard to find a reasonable and efficient path, and strive to bring new drugs to patients as soon as possible .
In the future, we will continue to accelerate the global simultaneous research and development and launch of more high-incidence tumor drugs in China .
"

As the world's leading multinational pharmaceutical company, Novartis has a number of lung cancer treatment drugs approved
.
Novartis is committed to improving the accessibility of innovative medicines, so that more Chinese patients can benefit from innovative results as soon as possible, bringing them health and hope
.

References

1.
Planchard D , Smit EF, Groen HJM, et al.
Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial.
Lancet Oncol.
2017 Oct;18 (10):1307-1316.
doi: 10.
1016/S1470-2045(17)30679-4.

2.
Planchard D , Besse B, Groen HJM, et al.
Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial.
Lancet Oncol.
2016 Jul;17(7):984-993.
doi: 10.
1016/S1470-2045(16)30146-2.

3.
Odogwu L , Mathieu L, Blumenthal G, et al.
FDA Approval Summary: Dabrafenib and Trametinib for the Treatment of Metastatic Non-Small Cell Lung Cancers Harboring BRAF V600E Mutations.
Oncologist.
2018 Jun;23(6):740-745 .
doi: 10.
1634/theoncologist.
2017-0642.

4.
AULIAC JB , BAYLE S, DO P, et al.
Efficacy of dabrafenib plus trametinib combination in patients with BRAF V600E-mutant NSCLC in real-world setting: GFPC 01-2019 [ J ] .
Cancers (Basel), 2020, 12 (12): E3608.

5.
AULIAC JB , BAYLE S, DO P, et al.
Efficacy of dabrafenib plus trametinib combination in patients with BRAF V600E-mutant NSCLC in real-world setting: GFPC 01-2019 [ J ] .
Cancers (Basel), 2020, 12 (12): E3608.

6.
Chinese Society of Clinical Oncology .
Guidelines for the diagnosis and treatment of non-small cell lung cancer ( 2021) [ M ] .
Beijing : People's Health Publishing House , 2021.
Chinese Society of Clinical Oncology.
Guidelines for diagnosis and treatment of non-small cell lung cancer (version 2021 ) [ M ] .
Beijing: People's Medical Publishing House, 2021.

7 , Zhao Yuanyuan, Zhou Jianying , Fan Yun , et al.
Advances in the treatment of BRAF V600 mutant non-small cell lung cancer [J].
China Oncology , 2021, 31(12):8.

7 , Zhao Yuanyuan, Zhou Jianying , Fan Yun , et al.
Advances in the treatment of BRAF V600 mutant non-small cell lung cancer [J].
China Oncology , 2021, 31(12): 8.
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