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Indications expanded to early lung cancer … Benefits remain ‘secondary’ treatment of advanced lung cancer
National Cancer Center Chief Investigator Ji-Yeon Han, “It is essential to use good treatment first.”
“It is the foundation of chemotherapy to use the best treatment first.”
While Tagriso (ingredient name osimirtinib, AstraZeneca), a third-generation EGFR-targeted non-small cell lung cancer drug, expanded its indications to early lung cancer in Korea, it was based on the wage standard that still remains. in the secondary treatment of patients with advanced lung cancer. lung cancer.
On the 19th, AstraZeneca Korea (CEO Sangpyo Kim) held a press conference to commemorate the approval of Tagriso’s fifth anniversary of its launch in Korea and the first surgical aid for the treatment of non-small cell lung cancer.
At this meeting held online because of Corona 19, Chief Investigator Han Ji-yeon from the National Cancer Center and Professor Hong Min-hee from the Department of Oncology at Yonsei University reviewed the current status of lung cancer and major clinical studies of Taris Riso from AURA to FLAURA and ADAURA, and their significance.
Tagriso is a third generation epidermal growth factor receptor (EGFR) inhibitor. It has a higher selectivity for EGFR-sensitive mutations (Exon19del, L858R) than first and second generation EGFR inhibitors. There are relatively few side effects that can occur.
Furthermore, unlike 1st and 2nd generation EGFR inhibitors, it has a high permeability of the blood brain barrier (BBB) and acts effectively on the T790m mutation, a major mutation caused by 1st and 2nd generation EGFR inhibitors .
Based on these effects, Tagriso demonstrated superior efficacy and safety compared to standard treatment (pemetrexed + platinum chemotherapy) in the AURA clinical trial for non-small cell lung cancer patients with advanced disease after prior treatment with EGFR inhibitors. It has obtained FDA approval as a second-line treatment for advanced non-small cell lung cancer.
In the subsequent FLAURA study, patients with no prior experience of EGFR inhibitor treatment were directly compared with first-generation EGFR inhibitors to demonstrate superior improvement in overall survival (OS), and the National Comprehensive Cancer Network (Red Comprehensive Cancer Institute) became the first EGFR inhibitor recommended in the guidelines.
Additionally, last year, it demonstrated superior efficacy and safety as adjunctive therapy after surgery in patients with early lung cancer (1b, 2, 3) among targeted treatments for non-small cell lung cancer.
The main reason Tagriso was able to expand its indications to early lung cancer beyond first and second generation EGFR inhibitors was the inhibitory effect on central nervous system (CNS) recurrence.
Unlike first and second generation EGFR inhibitors, which cannot cross the cerebrovascular barrier, tagrysum has a high permeability to the cerebrovascular barrier, making it effective in treating patients with metastases in the central nervous system and in the prevention of metastases in the central nervous system.
Based on this, in the ADAURA study, Tagrisso raised the disease-free survival rate (DFS) to the extent that there were no significant differences for each stage.
In this regard, Professor Hong Min-hee of Yonsei University Medical University gave meaning to “Tagriso has changed the natural course of lung cancer.”
Furthermore, he emphasized, “The reduction in the risk of disease progression by more than 80% compared to the control group is an unprecedented result among targeted therapy studies.”
In fact, the ADAURA study showed significant differences in the effect of Tagriso’s treatment compared to the control group and ended early, and the review committee assessed it as “an overwhelming difference” at that time.
Based on this differential treatment effect, Targriso’s indications are moving toward early lung cancer beyond primary treatment for advanced lung cancer, but the national wage standard remains secondary treatment.
One of the main reasons is related to the subanalysis of the FLAURA study. In Asians, the effect of improving survival time in first-line treatment was not significant.
However, experts believe this is due to the heterogeneous pattern of clinical practice in Japan, which accounted for the absolute proportion of Asians who participated in the study.
Although the study was conducted in patients with unresectable stage 4 non-small cell lung cancer, resectable patients were included, that is, with a good prognosis, and the statistical difference was diluted with the control group.
In particular, since more of these patients were included in the control group, Chief Investigator Han Ji-yeon’s analysis was that the data on Asians was diluted.
While the ADAURA study showed unprecedented efficacy of Tagriso in postoperatively administered patients, the FLAURA study included patients treated with EGFR inhibitors after surgery, leading to unpredictable results.
Furthermore, in Japan, the drug was switched to Tagriso even for small pneumonia lesions that are not of great clinical significance, and not a few patients in the control group continued treatment with Tagriso to reduce the statistical difference, according to chief researcher Han. Hee-yeon.
The hypothesis that the heterogeneous results of the FLAURA study sub-analysis are influenced by Japanese clinical patterns was advanced by the recently published FLAURA China study.
As a result of a study conducted in China with a design similar to the global standard, the effect of improving survival time in FLAURA was reconfirmed.
In this regard, lead researcher Han Ji-yeon said: “There have been many studies related to EGFR inhibitors so far, but few studies have reported differences in prognosis between races.” I think this was born. “
He added: “Because our country is proceeding with the treatment according to the global standard, it will be similar to the global data (instead of the Asian sub-analysis).”
In addition, he stressed that “the principle of cancer treatment is to use the best treatment first,” he said. “It is a good country to be able to give the best treatment to all patients first.”
In other words, it is pointed out that there is no reason to limit the coverage of Tagriso, which showed a stronger effect than first and second generation EGFR inhibitors, to second line treatment.
However, the treatment options available to patients who relapse after treatment with Tagriso are not yet adequate.
However, researcher Ji-Yeon Han said: “Only half of T790m mutation patients who can be treated with Tagriso after using first and second generation EGFR target treatments can be treated, and only some of them can Be treated”. the effect of the treatment is the best and it is not inferior even if it is analyzed in all aspects, it is correct to write it first ”.
On the other hand, in recent years candidates have also emerged one after another who show potential for resistance to tagriso.
Among them, Rekraza (ingredient name Razertinib, Yuhan Corporation), which recently gained approval as a second-line treatment for EGFR mutant non-small cell lung cancer, was tested in combination with the dual antibody EGFR-MET from Janssen amivantamab , in which 36% of the drug was resistant to tagriso in phase 1 clinical trials. The reaction rate was found to be demonstrated.
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