Researchers around the world are paying attention to the primary effect of Rexraza, a new lung cancer drug

On the 3rd, Professor Cho Byung-chul of Severance Hospital announces a study on LASER301, while lung cancer experts from around the world are watching.

A new domestic lung cancer drug, Lexraza (named Lazertinib), is on track to acquire the title of the world’s second third-generation EGFR-TKI (Epithelial Growth Factor Receptor-Tyrosine Kinase Inhibitor) first-line treatment in the world.

Professor Cho Byeong-cheol of Severance Hospital’s Department of Oncology announced the final results of the LASER301 study involving 96 hospitals in 13 countries worldwide at ESMO-ASIA on the 3rd.

As a result, initial treatment with Lexraza in patients with EGFR-mutant non-small cell lung cancer was found to reduce the “risk of disease progression and death” by 55% compared with first-generation gefitinib.

The confirmed progression-free survival (PFS) of the lazertinib treatment group in this study was 20.6 months, which was more than double that of the gefitinib control group, which was 9.7 months.

Notably, it also left a new possibility and record that the progression-free survival period could exceed 20 months. Once the primary target endpoint is met, approval of the national and international indication as primary treatment is expected to proceed smoothly.

Asians, genetic subanalysis all successful

The published LASER301 study evaluated a significant portion of the FLAURA study, the primary treatment study for osiminitinib, so research design criteria (protocol), such as patient composition, are similar.

The total number of patients participating was 393, which is slightly lower than in the FLAURA study, but the ratio is similar. The Asian participation rate was 66% (vs. 62%) and there was no significant difference in the proportion of patients with exon 19 or L858R replacement gene deficiency. The median age was set at 67 years.

MAIN RESULTS OF THE LASER301 AND FLAURA STUDIES

The Asian sub-analysis was also disclosed, which was the focus of this study. 20.6 months in the lazertinib treatment group and 9.7 months in the gefitinib treatment group, the same study outcomes as in the entire patient group and, consequently, the risk of disease progression and death in patients treated with Lazertinib was 54% minor.

Regardless of gene classification, the effect was consistently found.

In the group of patients with the 19DEL gene (20.7 months vs. 10.9 months) and in the group of patients with the L858R gene (17.8 months vs. 9.6 months), the risk of disease progression and death was reduced by 54% and 59%, respectively. , confirming the strong third generation EGFR-TKI aspect.

Furthermore, the group of patients with brain metastases also showed a difference in progression-free survival of 16.4 months and 9.5 months, demonstrating a 58% improvement in the relative survival rate.

As a result, Lazertinib is poised to be reborn as a potent third-generation first-line EGFR-TKI treatment that exhibits uniform effects regardless of race, genetic classification, or brain metastases.

The side effects of lazertinib identified in the study were mainly rash, diarrhea, paraesthesia and increased liver levels, but most were mild and similar to the control group, gefitinib. There weren’t many grade 3 or higher side effects that were problematic.

“A strong domestic drug EGFR-TKI was born – said Cho Byeong-cheol, professor of oncology at Severance Hospital who presented the study – It is a drug with excellent effects and few side effects. It’s especially effective in Asians,” he said.

Notably, he said, “the strong inhibitory effect confirmed in the initial clinical trial was also confirmed in the final clinical trial,” adding, “That means there is a difference between the three generations.”

Answers from leading Korean and foreign researchers

Ben Solomon, a professor at the University of Melbourne Medical School in Australia who attended as a keynote speaker, said: “The Lazertinib effects announced so far appear to be consistent and have few side effects.” Based on this finding, we look forward to the study results of MARIPOSA, a combination therapy with amivantamab.”

A joint interview was conducted with Professor Byung-Cheol Cho and Dr Roth.

Dr Ross Su, National Cancer Center Singapore, said: ‘(The results) were so amazing. It was a very pleasant surprise. ‘The effect was impressive,’ he said.

He continued, “Based on these data, it seems likely that global approval will be possible. As this was an internationally initiated Phase 3 clinical trial following Osimertinib, we do not expect major hurdles. Mariposa 1 and 2 studies and Chrysalis 1 and 2 have already been conducted in the U.S. As it is progressing, U.S. approval is also no obstacle in that regard.”

Professor Ben said: ‘It can be upgraded to the primary standard treatment option. There are no obstacles in the process of adding to the NCCN, ASCO and ESMO guidelines. As various studies of Lazertinib are ongoing, it is an important foundation drug. for the future third generation TKI drug.

There was also great interest in adverse reactions.

Professor Cho pointed out: ‘There was a question about paresthesia, but the important point is that it can be resolved by reducing the drug, and the crucial point is that there has been no discontinuation of the drug.’ Dr Roth said: “Osimertinib also has cardiotoxicity. Each drug has a different molecular structure, so the quirks show up as side effects, but it’s important that there isn’t a significant drug disruption.”

It is expected that there will be no major problems with the possibility that the overall survival rate data is not effective due to crossover (replacement of effective drugs) or the drug is undervalued because of this.

Professor Roth said: ‘Even if the survival data are not clinically valid, there is no devaluation of the drug. The main indicator is the progression-free survival period and the overall survival rate depends on the type of treatment and how to balance the effect of the drug. I understand that, so it doesn’t really matter.”

Kim Yeol-hong, a professor of oncology at Koryoan Hospital, whom we met on the spot, said: “We can evaluate it from two perspectives. Its peculiarity is that it showed the most convincing effect in patients with the L858R gene, and also showed a strong tumor suppressing effect in patients with brain metastases. It’s important that good data is created in this area,” he said.

On the other hand, regarding the issue of reimbursement promotion, Professor Cho said, ‘As evidence has emerged for the first-line treatment of lazertinib, if it enters the reimbursement stage after approval, there is a high possibility that we will look into it together. We have to do it again.”

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