Osimertinib was approved for first-line treatment

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

Osimertinib is approved for first-line treatment of adult patients with EGFR mutation-positive advanced or metastatic non-small cell lung cancer, which means that there are more options for the treatment of patients with EGFR mutation-positive advanced or metastatic non-small cell lung cancer. In fact, Tagrisso was not approved for the first time in China. As early as March 2017, it was approved in China. Tagrisso, as a third-generation targeted drug for lung cancer, is used to treat the disease progression during or after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) and 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 of the past can benefit from the patients, there are not many patients who can actually use the drug. According to the FLAURA study PRO 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 were eligible for second-line treatment. In the second-line treatment, not all patients have T790M mutations, so only 43% of patients who can use the third-generation targeted drug Tagrisso in second-line therapy. Taken together, the final second-line patients who used the third-generation EGFR-TKI targeting drug, Osimertinib (Tagrisso), were only 19.78%. Therefore, upgrading from second-line treatment to first-line treatment is of great significance and means that more patients will benefit from the drug.

Tagrisso was approved for first-line treatment, primarily based on a large phase 3 double-blind clinical trial called FLAURA. The trial enrolled more than 500 patients (more than 60% of whom were of Asian descent) who were newly diagnosed with advanced or metastatic non-small cell lung cancer with EGFR-sensitive mutations and had not yet been treated for advanced lung cancer. The patients were randomly assigned to receive first-generation EGFR-targeted therapy (currently standard) or third-generation targeted drug Tagrisso. The results showed that Tagrisso was significantly more effective in progression-free survival (PFS) than standard therapy (Tagrisso VS standard therapy = 18.9 months VS 10.2 months, which is almost one more time). For median duration of remission, Tagrisso VS standard therapy = 17.2 months VS8.5 months. This suggests that Tagrisso has fewer serious adverse reactions and a reduced overall risk of death, and previous studies have shown that Tagrisso is more effective in comparison.

There are currently 6 EGFR targeted drugs marketed, one generation of Gefitinib, Erlotinib and Icotinib, the second generation of Afatinib and Dacomitinib, three generations of Osimertinib. Currently, there are three clinical treatment modes, which are: 1+3 (first generation, sequential 3 generation after drug resistance), 2+3 (sequential 3 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 fewer patients actually complete “2+3” than “1+3″, less than 10%. In the ARCHER1050 study, the proportion of patients with 3-generation sequential dacinib TKI was 9.7%. In addition, the adverse reactions of the second-generation TKI were significantly more serious than those of the first-generation and third-generation TKI, which involved a wide range of targets. The two modes of 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/ chemotherapy mode, which can only bring benefits to a few patients. For patients with no financial burden and high quality of life requirements, 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.