On September 30, 2022, the online journal OncLive Medical published the results of the Phase III ANEAS trial (NCT03849768), which evaluated the efficacy and safety of ametinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) carrying EGFR mutations.
Previously, in March 2020, ametinib was approved for marketing by the China National Medical Products Administration for the treatment of locally advanced or metastatic NSCLC patients with who have previously progressed with EGFR-TKI treatment and T790M mutation positive .
Figure Note: The third generation EGFR-TKI data list; the orange background is the approved solution.
EGFR mutation is a common oncogenic driver of non-small cell lung cancer . The demand for third-generation EGFR inhibitors remains effective first-line and well tolerated. Ametinib is the first Chinese original third-generation EGFR-TKI innovative drug , independently developed by Hausen Pharmaceutical. It is also the world's first third-generation EGFR-TKI with a median progression-free survival (PFS) of more than 1 year (used in the second line).
Product name: Amele
Generic name: Ametinib (Almonertinib)
Code number: HS-10296
Target: EGFR
The United States was approved for the first time: Not approved
China was approved for the first time: March 2020
Approved indication: Adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have progressed after treatment with other EGFR-positive lung cancer targeted drugs and have positive T790M mutations.
Recommended dosage: 110mg (2 tablets), once a day, with or without meals.
Specifications: 55mg*20 tablets
Is medical insurance?: has been included in medical insurance
Storage conditions: Save below 130℃
Clinical data
In this randomized, double-blind trial, a total of 429 Chinese patients were included. The enrolled patients were randomly assigned at a 1:1 ratio and received treatment with 110 mg of ametinib (n=214) and 250 mg of gefitinib (n=215) per day, respectively.
Patients were stratified according to EGFR mutation type (exon 19 deletion VS L858R) and central nervous system (CNS) metastatic state (with VS without). Patients receive study medication until disease progression, withdrawal of consent, unacceptable toxicity, or other discontinuation criteria are met. The baseline characteristics of the enrolled patients include: the median age is 62 years old; most of the patients are female and are all Asian. Overall, 65.4% (n=140) of patients had EGFR exon 19 deletion, 34.6% (n=74) of patients had EGFR L858R mutation; 65.6% (n=141) of EGFR exon 19 deletion, 34.4% (n=74) of patients had EGFR L858R mutation. In addition, in the ametinib group and the gefitinib group, central nervous system metastasis occurred, respectively. The primary endpoint of the for the
trial was the progression-free survival (PFS) evaluated by the investigator; the secondary endpoint of includes overall survival (OS), objective response rate (ORR), duration of remission (DOR), and disease control rate (DCR).
data As of January 15, 2021, all randomized patients received at least 1 dose of ametinib. In addition, 19.1% (n=41) of patients in the gefitinib group had received at least 1 dose of ametinib.
Ametinib group VS The median duration of total drug exposure in the gefitinib group was 463.5 days vs 254.0 days; drug adherence was 99.3% VS 98.5% . At the end of data, 43.5% (n=93) and 15.8% (n=34) of patients were still receiving treatment in the ametinib group and the gefitinib group, respectively.The results of the
trial showed that the median follow-up time of the ametinib group VS gefitinib group was 20.5 months VS 20.7 months , the median progression-free survival (PFS) was 19.3 months VS 9.9 months , the 1-year PFS rate was 69.5% VS 46.3% , and the 2-year PFS rate was 32.5% VS 12.9% .
In addition, the PFS benefit of ametinib was shown to be consistent with all pre-identified stratification factors, including EGFR mutation type and central nervous system (CNS) metastasis status.
In the subset of patients with EGFR exon 19 deletion, the median PFS of the ametinib group VS gefitinib group was 20.8 months VS 12.3 months ; among patients with EGFR L858R mutation, the median PFS of the ametinib group VS gefitinib group was 13.4 months VS 8.3 months .
In patients with CNS metastasis, the median PFS in the ametinib group VS gefitinib group was 15.3 months vs 8.2 months ; in patients without CNS metastasis, the median PFS in the ametinib group VS gefitinib group was 19.3 months vs 12.6 months . When the
data is cut off, the median overall survival (OS) of the two groups cannot be evaluated. The 12-month OS rate in the ametinib group VS Gefitinib group was 86.2% VS 85.3% .
Ametinib group VS Gefitinib group The objective response rate (ORR) was 73.8% VS 72.1% ; the disease control rate (DCR) was 93.0% VS 96.7% ; the median response duration (DOR) was 18.1 month VS 8.3 month .
Adverse reactions
In terms of safety, 98.8% (n=424) of patients experienced at least 1 adverse reaction during the study treatment period. The most common adverse reactions in the ametinib group and gefitinib group include: serum creatine phosphokinase (35.5% VS 9.3%), aspartate aminotransferase (29.9% VS 54.0%), alanine aminotransferase (29.4% VS 55.8%), rash (23.4% VS 41.4%), and diarrhea (16.4% VS 35.8%).
In addition, in the ametinib group and the gefitinib group, 98.6% (n=211) and 99.1% (n=213) of patients experienced at least one treatment-related emergency adverse reaction. The most common treatment-related emergency adverse reactions were alanine aminotransferase elevated (2.8% VS 12.1%) and aspartate aminotransferase elevated (1.4% VS 9.3%).
Summary
These results show that compared with gefitinib, ametinib significantly prolongs the progression-free survival of patients with initial treatment of locally advanced or metastatic EGFR mutations in non-small cell lung cancer. This also shows that ametinib can be used as the first-line treatment option for in patients with EGFR mutation non-small cell lung cancer.
Reference source:
https://www.onclive.com
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