▎WuXi AppTec Content Team Report

On June 26, the official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China announced,AstraZenecaThe Third Generation EGFR-TKI Osimertinib Mesylate TabletsProposed for inclusion in the priority review, intended for use in patients who have not experienced disease progression during or after receiving platinum-based chemoradiotherapy, withEGFRExon 19 deletion or exon 21 (L858R) Substitution mutation in locally advanced, unresectable (Stage III) non-small cell lung cancerTreatment of adult patients with NSCLC.

According to the recent results of the LAURA Phase 3 study published by AstraZeneca, compared with placebo after chemoradiotherapy, in patients withEGFRExon 19 deletion or exon 21 (L858R) In III-stage unresectable NSCLC patients with substitution mutations, osimertinib demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS),Extended PFS by more than three years and reduced the risk of disease progression or death by 84%.。These results were presented at the plenary session of the 2024 American Society of Clinical Oncology (ASCO) and simultaneously published in The New England Journal of Medicine.

Screenshot source:CDE Official Website

LAURA is a randomized, double-blind, placebo-controlled, global multi-center Phase III clinical study, with participants beingStage III unresectableEGFRMutant Non-Small Cell Lung CancerThese patients did not experience disease progression after receiving platinum-based chemoradiotherapy. Patients received 80 mg of oral osimertinib tablets once daily until disease progression, intolerable toxicity, or meeting the discontinuation criteria. After disease progression, patients in the placebo group could continue to receive osimertinib treatment.The trial was conducted at 145 centers across more than 15 countries and regions, including the United States, Europe, South America, and Asia, with a total of 216 patients enrolled.This analysis focuses on the primary endpoint, PFS.The study will continue to evaluate the secondary endpoint of overall survival (OS).

According to the previous press release by AstraZeneca, the results assessed by the Blinded Independent Central Review (BICR) showed,Compared with placebo, osimertinib reduced the risk of disease progression or death by 84%.. Patients in the osimertinib treatment groupThe median PFS was 39.1 months, while the median PFS for patients receiving placebo treatment was 5.6 months.. More importantly, across all predefined subgroups, including gender, race,EGFRMutation type, age, smoking history, and prior response to CRT treatment all demonstrated clinically meaningful PFS benefits.

Moreover, the OS data trend for Osimertinib is positive, although the data were not yet mature at the time of this analysis. The safety profile and discontinuation rate due to adverse events (AEs) were consistent with expectations, and no new safety concerns were identified. In the Osimertinib group, 35% of patients experienced grade ≥3 adverse events from any cause, compared to 12% in the placebo group.

Previously, Susan Galbraith, Executive Vice President of AstraZeneca Global and Head of Oncology R&D, stated in a press release that osimertinib can extend the progression-free survival period by more than three years for these potentially "curable" lung cancer patients, highlighting the necessity of early detection and diagnosis for patients. These practice-changing data demonstrate osimertinib's role asEGFRThe Powerful Impact of Mutational Lung Cancer Cornerstone Therapy, Especially for Early Patients Who Have Progressed After Radiotherapy and Chemotherapy.

Osimertinib is an irreversible third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). This product has currently been approved for four indications in China:

1) For patients who have previously experienced disease progression during or after EGFR-TKI treatment, and haveEGFR T790MSecond-line treatment for locally advanced or metastatic NSCLC with mutations;

2) Used for havingEGFRExon 19 deletion or exon 21 (L858R) First-line treatment for patients with locally advanced or metastatic NSCLC harboring substitution mutations;

3) Used for havingEGFRExon 19 deletion or exon 21 (L858R) Adjuvant treatment for stage IB-IIIA NSCLC after radical surgery (with or without adjuvant chemotherapy as determined by the physician);

4) In combination with pemetrexed and platinum-based chemotherapy drugs for patients withEGFRExon 19 deletion or exon 21 (L858R) Localized advanced or metastatic substitution mutationNSCLCAdult PatientsFirst-line treatment。

References:

[2] Heavyweight | Tagrisso® (泰瑞沙®), the world's first third-generation EGFR-TKI lung cancer targeted drug, receives approval in China for first-line treatment of EGFR-mutated advanced non-small cell lung cancer in combination with chemotherapy.  Retrieved June 26，2024, From https://mp.weixin.qq.com/s/E8NE6UVBf9BwC25tBPUWdw

[3] In the LAURA III Phase clinical trial, compared with placebo, Tagrisso reduced the risk of disease progression or death by 84% in patients with EGFR-mutated Stage III inoperable lung cancer..  Retrieved June 26，2024, From https://mp.weixin.qq.com/s/6QoLqN5vY-KYpV5G54G5Gw