Osimertinib was approved for first-line treatment

The third-generation EGFR inhibitor, Osimertinib (Tagrisso, AZD9291), was approved by the Chinese Food and Drug Administration (NMPA) recently for first-line treatment of patients with EGFR mutation-positive advanced or metastatic non-small cell lung cancer (NSCLC), marking another milestone for treatment of EGFR-positive lung cancer in China.

Including Osimertinib, several treatment options exist for treating adult patients with EGFR mutation-positive advanced or metastatic non-small cell lung cancer. In fact, Osimertinib was not approved initially in China until the early March in 2017. As a third-generation drug for lung cancer, Osimertinib is used during or after treatment with epidermal growth factor receptor (EGFR) and tyrosine kinase inhibitor (TKI) for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are confirmed to have EGFR T790M positive mutations. But in the past, it has been approved as a second-line treatment for non-small cell lung cancer.

Although the second-line treatment can benefit the patients, not many patients can actually use the drug. According to the data reported at the European Lung Cancer Congress last April, only 46% of patients who failed a first-generation EGFR-targeted drug treatment in the first-line treatment were eligible for second-line treatment. During second-line treatment, not all patients have T790M mutations, so only 43% of patients are eligible to use Osimertinib. Taken together, only about 19.78% of patients were able to use Osimertinib. To allow more patients to benefit from the drug, it was necessary to upgrade Osimertinib to first-line treatment from the second-line treatment.

After a large phase 3 double-blind clinical trial FLAURA, Osimertinib was finally approved for the first-line treatment. The trial enrolled more than 500 patients (more than 60% were Asian descent) who were newly diagnosed with advanced or metastatic non-small cell lung cancer with EGFR-sensitive mutations and have not yet been treated for advanced lung cancer. The patients were randomly assigned to receive first-generation EGFR-targeted therapy (currently standard) or Osimertinib. Results showed that Osimertinib was significantly more effective in progression-free survival (PFS) than standard therapy (Tagrisso VS standard therapy = 18.9 months VS 10.2 months). For median duration of remission, Tagrisso VS standard therapy = 17.2 months VS 8.5 months. This suggests that Osimertinib is not only more effective compared to the standard therapy, but has fewer serious adverse reactions and a reduced overall risk of death.

There are currently 6 EGFR-targeted drugs on the market, including the first generation GefitinibErlotinib and Icotinib, the second generation Afatinib and Dacomitinib, and the third generation Osimertinib. Three clinical treatment options are: 1+3 (first generation, sequential 3rd generation after drug resistance), 2+3 (sequential 3rd generation after drug resistance), and 3+X (other treatment for the symptom after treatment progress of the third generation). From the available data, it seems that less than 10% of patients actually complete “2+3” compared to “1+3″. In the ARCHER1050 study, the proportion of patients with 3rd generation sequential dacinib TKI was 9.7%. In addition, the adverse reactions from the 2nd generation TKI were significantly more serious than those of the first-generation and third-generation TKI, which involved a wide range of targets. The “1+3” and “2+3” have prominent problems, that is, most patients do not use oxitinib eventually, and the ideal 1+3 and 2+3 are reduced to 1/2+0/, which can only benefit few patients. For patients without financial burden and want high quality of life, the first-line treatment of Osimertinib is preferred.


1. Soria, J. C. , Ohe, Y. , Vansteenkiste, J. , Reungwetwattana, T. , Chewaskulyong, B. , & Lee, K. H. , et al. (2018). Osimertinib in untreated egfr-mutated advanced non-small-cell lung cancer. The New England journal of medicine, 378(2), 113.

2. Mok, T. S. , Wu, Y. L. , Ahn, M. J. , Garassino, M. C. , Kim, H. R. , & Ramalingam, S. S. , et al. (2017). Osimertinib or platinum–pemetrexed in\r, egfr\r, t790m–positive lung cancer. New England Journal of Medicine, 376(7), 629-640.