AstraZeneca's Osimertinib Receives NMPA Approval in China for Adjuvant Treatment of Early-Stage EGFR-Mutated Non-Small Cell Lung Cancer

Source: Pharma Horizon

On April 14, 2021, AstraZeneca announced that the China National Medical Products Administration (NMPA) had formally approved the targeted therapy Tagrisso (osimertinib mesylate tablets) for the treatment of patients with stage IB–IIIA non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. Patients must have previously undergone surgical resection, with or without adjuvant chemotherapy, as determined by their physician.

The NMPA approval is based on the positive results of the ADAURA study. The trial demonstrated that osimertinib provided statistically significant and clinically meaningful disease-free survival (DFS) benefits in both the primary study population of patients with stage II and IIIA EGFR-mutated non-small cell lung cancer (EGFRm NSCLC) and in patients with stage IB–IIIA disease, a secondary endpoint population. According to the press release, osimertinib is the only targeted therapy to demonstrate efficacy in early-stage lung cancer in global clinical studies and the first such agent approved in China. The “unprecedented results” from the phase III ADAURA clinical trial showed that osimertinib reduced the risk of disease recurrence or death by 80%.

Lung cancer is the leading cause of cancer-related deaths in both men and women, accounting for approximately one-fifth of all cancer fatalities. Lung cancer is typically classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with NSCLC comprising 80%–85% of cases. The majority of NSCLC patients are diagnosed at an advanced stage, while only about 25%–30% of patients are eligible for surgical resection at the time of diagnosis. Although up to 30% of NSCLC patients can be diagnosed at an early stage and undergo potentially curative surgery, disease recurrence remains common even in early-stage disease. According to historical data, nearly half of patients with stage IB disease and more than three-quarters of those with stage IIIA disease experience recurrence within five years. Approximately 10%–15% of NSCLC patients in the United States and Europe harbor epidermal growth factor receptor (EGFR) mutations (EGFRm), whereas this proportion reaches as high as 30%–40% among Asian patients. These patients are particularly sensitive to treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs), which block the signaling pathways driving tumor cell growth.

The ADAURA study results demonstrated that adjuvant osimertinib reduced the risk of disease recurrence or death, the primary endpoint of disease-free survival (DFS), by 83% in patients with stage II and IIIA disease (hazard ratio [HR] 0.17; 99.06% confidence interval [CI] 0.11–0.26; p<0.001). In the overall study population comprising patients with stage IB–IIIA disease, DFS results showed that osimertinib reduced the risk of disease recurrence or death by 80% (HR 0.20; 99.12% CI 0.14–0.30; p<0.001). Consistent DFS benefits were observed across all prespecified subgroups, including Asian and non-Asian patients, regardless of prior use of adjuvant chemotherapy. The safety and tolerability profile of osimertinib in this study was consistent with previous studies in metastatic non-small cell lung cancer (NSCLC). These findings have been published in the New England Journal of Medicine (NEJM).

Currently, osimertinib has been approved in more than a dozen countries and regions, including the United States, for the treatment of early-stage lung cancer, and discussions regarding indication applications in other parts of the world are ongoing. In the United States, Japan, China, the European Union, and many other countries and regions, osimertinib is also approved for first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutations (EGFRm), as well as for the treatment of patients with locally advanced or metastatic NSCLC carrying the EGFR T790M mutation. Previously, the marketing application for this new indication of osimertinib was included in the priority review and approval program by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration. This approval marks the third indication for osimertinib in China, following its previous approvals for second-line treatment of NSCLC with EGFR T790M mutations and for first-line treatment of EGFRm NSCLC, both of which have already been included in the National Reimbursement Drug List.

Note: The original text has been abridged.