AstraZeneca’s third-generation EGFR mutant non-small cell lung cancer treatment’Tagriso (ingredient name osimertinib)’ is presented as a standard treatment regimen in various stages from early (1B-3A) to advanced/metastatic stage 4, and the history of lung cancer treatment It is a representative anticancer drug that is newly using
However, in Korea, due to controversy over the effects in Asians, the entry of the benefit right to the advanced stage primary treatment has failed frequently, and the most recent postoperative adjuvant therapy approved by the Ministry of Food and Drug Safety has received mixed evaluations from domestic lung cancer experts and is actually applied clinically. Difficulties are expected.
Accordingly,’Tagriso’ in the domestic lung cancer treatment environment from Chief Researcher Han Ji-yeon of the National Cancer Center Lung Cancer Center and Professor Hong Min-hee of the Lung Cancer Center of Yonsei Cancer Center, who attended the’Press Conference to Commemorate the 5th Anniversary of Tagriso Indication Expansion and Domestic Launch’ held on the 19th We heard about the clinical value of the drug and the issues that have been raised so far.
“Tagriso brings unprecedented benefits to patients such as brain metastasis”
Chief Researcher Ji-Yeon Han, who spoke as the speaker of the first session on this day, is the first third-generation targeted therapy targeting EGFR, one of the mutations common in non-small cell lung cancer patients in Korea, as a major landmark of the achievements that’Tagriso’ has achieved over the past five years. It was introduced through clinical trial data.
Chief Researcher Han Ji-yeon said, “In the phase 3 clinical AURA3 study that changed the paradigm of advanced non-small cell lung cancer treatment, Tagriso showed median progression-free survival (mPFS) more than twice as high as the conventional standard therapy.” At 10.1 months, compared to 4.4 months in the control group, the risk of disease progression and death was reduced by 70%.”
Since then, a top researcher focused on the value of the Phase 3 clinical FLAURA study, which presented the therapeutic benefits of Tagriso to more patients as a first-line treatment for advanced non-small cell lung cancer without confirmation of the T790M mutation.
One Chief Researcher said, “Tagriso is the only treatment that has demonstrated a significant median overall survival (mOS) of 3 years or more even with cross-administration allowed, as well as extending mPFS by 8.7 months from the previous 1st and 2nd generation target therapies in the FLAURA study. “The mOS of the tagriso-treated group was 38.6 months, lowering the risk of death by 20% compared to 31.8 months of the control group, and realizing unprecedented treatment benefits in the field of lung cancer treatment, the number one cancer death.”
In addition, “Tagriso’s treatment effect is inferior to brain metastases that are accompanied by 19-24% of patients with EGFR mutations, and PFS is about 8-14 months on average in the 1st and 2nd generation EGFR target therapies.” In addition to significantly improving PFS, EGFR mutation has become one of the best treatment options for non-small cell lung cancer, with or without central nervous system metastasis.
In addition, he opened his mouth about the results of the Asian sub-analysis of the FLAURA study, which was controversial in Korea. In the FLAURA study, Tagriso demonstrated an improvement in OS compared to the control group in all patient groups, but the Asian sub-analysis showed no difference from the control group with a risk ratio (HR) of 1.00.
In this regard, the opinion of Asians was suggested that the strategy of using tagriso as a first-line treatment option is not effective in prolonging the patient’s survival rate. In fact, it is known that the Cancer Disease Review Committee of the National Health Insurance Review and Assessment Service has repeatedly abolished the agenda for expanding Tagriso benefits for advanced primary treatment for this reason.
One Chief Researcher said, “If you look at the data from Japanese, who account for a large proportion of Asians in the FLAURA study, other countries were evaluated for patients in advanced stage, whereas in Japan, a large proportion of patients with recurrence after surgery with a relatively good treatment prognosis were included.” “In addition, due to the nature of Japan, which is sensitive to adverse interstitial pulmonary disease (ILD) reactions, only 10% of the Tagriso-administered group changed to other targeted anticancer drugs with only grades 1 and 2 ILDs, so it is estimated that there will be a bias in OS results. “I can do it,” he explained.
“Recently, for further research on this, an additional study of the Chinese was published, and as a result, data consistent with the PFS and OS benefits of Tagriso shown in the entire FLAURA study, the effect on Asians was resolved. “It is reasonable to use the most effective treatment for lung cancer with a high mortality rate and a poor prognosis,” he said. “There is no reason not to use Tagriso first.”
“Unprecedented DFS risk ratio, there is potential for future OS improvement”
Professor Hong Min-hee, who was the second speaker, introduced the major achievements of Tagriso’s Phase 3 clinical ADAURA study, which is the basis for’postoperative adjuvant therapy’, which has recently expanded its indications in Korea.
This study is a clinical trial that made’tagriso’ the first target anticancer drug available in the treatment of lung cancer for the purpose of cure.
Professor Hong Min-hee said, “In the ADAURA study, tagriso was used as an adjuvant therapy after surgery for patients with early stage (1B-3A) lung cancer, and the disease-free survival rate (DFS) of patients with stage 2 to 3A, which was set as the primary endpoint, was 24 months of Tagriso. It was 90% in the treatment group and 44% in the placebo group, reducing the risk of disease recurrence and death by 83%.” “It showed consistent DFS results regardless of stage and previous adjuvant chemotherapy.”
Professor Hong said, “Even in early stage lung cancer, recurrence occurs in more than 50% within 5 years after tumor resection, and the effect of improving the overall survival rate of 5 years of adjuvant chemotherapy in some IB and stage 2~3 patients is not using adjuvant chemotherapy. “Tagriso shows remarkable results in reducing the risk of recurrence or death by 80% compared to placebo in early stage (1B, 2, 3A) patients who underwent complete tumor resection through phase 3 clinical trials,” he said. An independent data monitoring committee of the Association of Clinical Oncology (ASCO) recommended early release of clinical data.”
Professor Hong emphasized that “Tagriso is the first case to present the therapeutic potential of EGFR targeted therapy in postoperative adjuvant therapy, and will open a new horizon in lung cancer treatment in the future.”
However, at the time of the publication of the results of the ADAURA research, domestic lung cancer experts expressed the opinion that premature judgments should be taken care of by comparing the results of the previous 1st and 2nd generation targeted anticancer drugs.
As a result of a CTONG study that evaluated the effects of postoperative adjuvant therapy of’gefitinib’, a first-generation treatment in the past, the DFS improvement was proven, but there was a case where the OS improvement failed as a result when the DFS curve rapidly dropped from the second year after the drug administration period ended. to be.
In this ADAURA study, the use of tagriso was administered for 3 years, and only data for the 2nd year are currently available. Therefore, it is necessary to examine whether or not tagriso adjuvant therapy will improve the patient’s overall survival rate as a result.
In response, Professor Hong said, “There is a clear difference between the ADAURA study and the CTONG study.” “First, the DFS risk ratio of tagriso shown in the ADAURA study is significantly lower than in the CTONG study. “It will affect the patient’s overall survival.”
As’gefitinib’ used in the CTONG study is less effective on brain metastasis than’tagriso’, it is an opinion that it may not have prevented brain metastasis with a poor prognosis in relapsed patients.
Professor Hong said, “Tagriso will be able to prevent brain metastasis by showing a higher permeability to the cerebral blood vessel barrier (BBB) than existing first- and second-generation treatments,” said Professor Hong. “The ADAURA study also allows cross-administration, demonstrating overall survival improvement. “This can be difficult, but there seems to be a possibility of improving survival due to the differences shown earlier.”