Indications expanded to early lung cancer…Benefits are still advanced lung cancer’secondary’ treatment
National Cancer Center Chief Researcher Ji-Yeon Han “It is basic to use good treatment first”
“Using the best treatment first is the basis of chemotherapy.”
While the third-generation EGFR-targeted non-small cell lung cancer drug Tagriso (ingredient names osimirtinib, AstraZeneca) expanded its indications to early lung cancer in Korea, it was sounded based on the salary standard that still stays in the secondary treatment of advanced lung cancer.
On the 19th, AstraZeneca Korea (CEO Sang-pyo Kim) held a press conference to commemorate the approval of Tagriso’s 5th anniversary of its launch in Korea and the first surgical aid for non-small cell lung cancer target treatment.
In this meeting held online due to Corona 19, Chief Researcher Han Ji-yeon of the National Cancer Center and Professor Hong Min-hee of the Department of Oncology at Yonsei University revised the current status of lung cancer and the major clinical studies of Taris Riso from AURA to FLAURA and ADAURA, and their meaning.
Tagriso is a third-generation epidermal growth factor receptor (EGFR) inhibitor, and it has higher selectivity to EGFR-sensitive mutations (Exon19del, L858R) than the first and second-generation EGFR inhibitors, thereby inhibiting normal epidermal growth factor receptors. There are relatively few side effects that can occur.
In addition, unlike the first and second generation EGFR inhibitors, it has a high blood brain barrier (BBB) permeability, and works effectively on the T790m mutation, a major mutation caused by the first and second generation EGFR inhibitors.
Based on these effects, Tagriso proved superior efficacy and safety compared to standard treatment (pemetrexide + platinum chemotherapy) in the AURA clinical trial for non-small cell lung cancer patients with advanced disease after previous treatment with EGFR inhibitors. It has obtained FDA approval as a second-line treatment for advanced non-small cell lung cancer.
Subsequent FLAURA studies demonstrated superior overall survival (OS) improvement effects in patients without previous EGFR inhibitor treatment experience, compared to first-generation EGFR inhibitors, and the National Comprehensive Cancer Network (National Comprehensive Cancer Network). , NCCN) became the first recommended EGFR inhibitor in the guidelines.
Furthermore, last year, it proved superior efficacy and safety as an adjuvant therapy after surgery in patients with early lung cancer (1b, 2, 3) among targeted treatments for non-small cell lung cancer. Obtained indications for.
The main reason Tagriso was able to expand its indications to early lung cancer beyond 1st and 2nd generation EGFR inhibitors was the inhibitory effect on the recurrence of the Central Nervous System (CNS).
Unlike the 1st and 2nd generation EGFR inhibitors that cannot cross the cerebrovascular barrier, tagriso has a high permeability to the cerebrovascular barrier, so it is effective in treating patients with central nervous system metastasis as well as preventing central nervous system metastasis.
Based on this, in the ADAURA study, Tagrisso raised the disease-free survival rate (DFS) to the extent that there was no significant difference for each stage.
In this regard, Professor Hong Min-hee of Yonsei University Medical University added meaning that “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 studies in targeted therapy.”
In fact, the ADAURA study showed significant differences in the treatment effect of Tagriso compared to the control group and ended early, and the review committee evaluated it as “an overwhelming difference” at the time.
Based on this differentiated treatment effect, Tagriso’s indications are advancing to early lung cancer beyond the first treatment for advanced lung cancer, but the domestic salary standard still remains at the second treatment.
One of the biggest reasons is related to the sub-analysis of the FLAURA study. In Asians, the effect of improving the survival time in the first-line treatment was not significant.
However, experts believe that this is due to the heterogeneous clinical practice pattern in Japan, which accounted for the absolute proportion of Asians participating in the study.
Although the study was conducted on patients with non-resectable stage 4 non-small cell lung cancer, patients with resectable, that is, with a good prognosis, were included, and the statistical difference was diluted with the control group.
In particular, as more of these patients were included in the control group, the analysis of Chief Researcher Han Ji-yeon was that the data on Asians were diluted.
While the ADAURA study showed unprecedented effectiveness of Tagriso in postoperatively administered patients, the FLAURA study included patients treated with EGFR inhibitors after surgery, producing unpredictable results.
In addition, in Japan, the drug was changed to Tagriso even for small pneumonia lesions that do not have a large 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 Jiyeon.
The hypothesis that the heterogeneous sub-analysis results of the FLAURA study are the influence of Japanese clinical patterns was fueled 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 the survival time in FLAURA was reconfirmed.
In this regard, Chief 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 treatment according to the global standard, it will be similar to the global data (rather than the Asian sub-analysis).”
Furthermore, he emphasized that “the principle of cancer treatment is to use the best treatment first,” he said. “It is a good country to be able to administer 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 the first and second generation EGFR inhibitors, to second-line treatment.
However, the treatment options available for patients who relapse after treatment with Tagriso are not yet adequate.
Nevertheless, researcher Ji-yeon Han said, “Only half of the T790m mutant patients who can be treated with Tagriso after using the first and second generation EGFR target treatments can be treated, and only some of them can be treated.” He emphasized that if the treatment effect is the best and is non-inferior even if analyzed in all aspects, it is correct to write it first.”
On the other hand, in recent years, candidates showing potential for resistance to tagriso are also emerging one after another.
Among them, Rekraza (ingredient name Razertinib, Yuhan Corporation), which recently obtained approval as a second-line treatment for EGFR mutant non-small cell lung cancer, was tested in combination with Janssen’s EGFR-MET double antibody amivantamab, in which 36% of tagriso resistance was achieved in phase 1 clinical trials. It was found that the reaction rate was shown.
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