On February 16, 2024, the U.S. Food and Drug Administration (FDA) approvedOsimertinib(Tagrisso, AstraZeneca Pharmaceuticals).In combination with platinum-based chemotherapy in the first line of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)** with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) replacement mutations**.
The indication approval is based on the results of the Flaura 2 (NCT04035486) study, which was published in the journal New England (NEJM), a top journal in medicine, in November 2023.
Let's take a look at some of the relevant aspects of the FLAURA2 study.
The FLAURA2 study is a global, multicenter, open-label, randomized controlled phase clinical study to evaluate the efficacy and safety of osimertinib in combination with pemetrexed and platinum-based chemotherapy compared to osimertinib monotherapy** in patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR-sensitive mutations (exon 19 deletion mutations or exon 21 L858R point mutations).
A total of 557 patients were randomized in a 1:1 ratio to osimertinib plus chemotherapy (pemetrexed and platinum) (279 patients) and osimertinib monotherapy** (278 patients). The primary endpoint was progression-free survival (PFS), with key secondary endpoints including overall survival (OS), objective response rate (ORR), duration of response (DOR), and disease control rate (DCR).
The median follow-up time in the combination chemotherapy group and the single-agent group was 19., respectively5 months and 165 months.
The results showed that the progression-free survival of osimertinib plus chemotherapy was significantly longer than that of osimertinib alone, and the median duration of response in the combination ** group was nearly 9 months higher than that in the monotherapy group (24 versus 15.).3 months), median progression-free survival was extended by 88 months (25.)5 months vs. 167 months), it was concluded that osimertinib in combination with chemotherapy in the first-line ** significantly prolonged progression-free survival compared with monotherapy. For.
The first-line ** of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletion or exon 21 (L858R) replacement mutations offers a new option.
In terms of safety, the incidence of grade 3 or higher adverse events was indeed higher in the combination chemotherapy group, but these adverse events were all known chemotherapy-related adverse events, and no new adverse events appeared.
Osimertinib is a third-representative epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that potently and selectively inhibits EGFR-TKI-associated resistance mutations, and is also effective in EGFR-mutated non-small cell lung cancer (NSCLC) with brain metastases, making it a first-line agent for patients with advanced EGFR-mutant NSCLC.
However, even osimertinib will inevitably face the problem of drug resistance, so how to effectively improve the initial efficacy so that patients can obtain better survival benefits? Combination chemotherapy is one of these pathways. Osimertinib in combination with chemotherapy was also approved for first-line use in patients with advanced EGFR mutations in NSCLC due to the superior efficacy of osimertinib in combination with chemotherapy and a favorable safety profile in the FLAURA2 study.
This approval is the fourth indication approved by the FDA for osimertinib, and the first three approved indications are:
1) Patients with locally advanced or metastatic NSCLC** who have progressed on or after prior EGFR tyrosine kinase inhibitor (TKI)** and who have been tested to be positive for EGFR T790M mutation**;
2) First-line patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)** with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) replacement mutations**;
3) Adjuvant after resection of non-small cell tumors with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) replacement mutations**.
At present, the reimbursement scope of osimertinib in China is as follows:
Let's look forward to the inclusion of osimertinib combined with chemotherapy as soon as possible!