- The first EGFR-targeted drug to achieve irreversible binding to the target and to be effective against some rare EGFR mutations, known as second-generation EGFR-TKI;
- A wide range of patients with EGFR targets in the first line, as well as patients with squamous cancers for whom chemotherapy is not effective;
- A wide range of patients with EGFR targets in the first line, as well as patients with squamous cancers for whom chemotherapy is not effective
- Outperforms chemotherapy and first-generation EGFR-targeted agents in patients with specific mutation types.
Afatinib is a second-generation lung cancer-targeting agent that targets the epidermal growth factor receptor (EGFR) target, primarily in patients with advanced non-small cell lung cancer (NSCLC) with sensitive mutations. Afatinib is a more potent anti-tumor agent than its first-generation counterpart, gefitinib, because it binds irreversibly to its target.
“Afatinib and gefitinib are both very effective targeted drugs, but afatinib works significantly better in patients who have survived more than 2 years, like a basketball game where the first half is tied and the second half is won by 20 points with afatinib. “Professor Tension, chief expert in lung cancer at the Cancer Hospital of Sun Yat-sen University, had this to say.
Afatinib has been launched in China after priority review
In February 2017, afatinib was approved for marketing in China by the former State Food and Drug Administration (CFDA), after receiving priority review status from the National Center for Drug Evaluation (CDE) on the grounds that “it is the first second-generation EGFR-TKI, which has obvious clinical advantages compared with the first-generation EGFR-TKI currently available in China “.
Afatinib is intended for use in (1) patients with advanced NSCLC with EGFR mutations and (2) patients with locally advanced or metastatic squamous lung cancer whose disease has progressed during or after platinum-containing chemotherapy.
The approval of afatinib was largely based on the results of the LUX-Lung series. The study found that in patients with advanced NSCLC with EGFR mutations, first-line treatment with afatinib prolonged median progression-free survival (PFS) by 5.4 months compared with standard chemotherapy (11 months versus 5.6 months), with the most common adverse events being diarrhea, rash, and onychomycosis, and other adverse events including acne and stomatitis and mucositis.
Afatinib irreversibly binds to targets and is more potent than generational drugs
“Choosing a targeted drug is like matching a key. “Professor Tension of the Center for Oncology Prevention and Control at Sun Yat-sen University described that this key should be tightly fitted and not give the signaling molecule a chance to bind. First-generation drugs bind reversibly to the receptor, which may mutate causing the drug to fail, that is, the key gradually becomes loose, and afatinib binds irreversibly.
In July 2013, afatinib was approved for marketing by the US Food and Drug Administration (FDA) for first-line treatment of metastatic NSCLC with EGFR mutations.
Alfatinib was marketed in the US and then in China nearly 4 years later, during which time several surprising results were achieved in clinical studies, including first-line treatment of NSCLC patients with EGFR mutations over chemotherapy and first-generation drugs, and second-line treatment of advanced squamous lung cancer that progressed after chemotherapy over first-generation drugs.
A clinical study directly comparing afatinib with gefitinib (LUX-Lung 7 study) showed that afatinib significantly reduced the risk of lung cancer progression and treatment failure by 27% as first-line therapy for patients with EGFR-mutated advanced NSCLC. After 2 years of treatment, the proportion of patients with progression-free survival was more than twice as high in the afatinib group as in the gefitinib group (18% and 8%, respectively). However, it is important to note that it also has a higher incidence and severity of adverse effects than the generation of drugs.
Afatinib treatment in Chinese patients is working well
Globally, 51.4% of lung cancer cases occur in Asia, with non-small cell lung cancer being the most common type, seen in more than 85% of cases, and 40% of Asian patients have specific EGFR gene mutations.
Afatinib is currently approved as first-line therapy for patients with EGFR mutation-positive NSCLC in more than 70 countries. “The most significant effect of afatinib is to allow significant tumor shrinkage, improved quality of life, and prolonged progression-free survival time. ” said Professor Tension. It is worth noting that more than half of the Asian subjects in the previously mentioned LUX-Lung7 clinical study were from China, accounting for about 20% of all subjects.
It is worth noting that the newly developed second-generation EGFR-targeted drug, daclatinib, is even more effective and is not yet available in China. In early April, the FDA accepted a new drug application for daclatinib for the first-line treatment of patients with locally advanced or metastatic NSCLC carrying EGFR mutations, and the FDA granted priority review status for this application; the European EMA also accepted its marketing application, and daclatinib was also given priority review by the CDE in China, with a high probability of simultaneous marketing at home and abroad.
In addition, when afatinib is resistant, if a T790m mutation is found, the third-generation targeted lung cancer drug oseltinib can be used.
Summary
Afatinib, a second-generation EGFR-targeted drug, has been approved in more than 70 countries, including China, and has demonstrated superiority over first-generation drugs in clinical studies and is recommended by guidelines for first-line treatment of advanced NSCLC with sensitive EGFR mutations.