When it comes to targeted therapy for lung cancer, many people can say one or two, such as “golden mutation”, “diamond mutation”, such as first-generation, second-generation, and third-generation targeted drugs. Compared with lung cancer patients without sensitive gene mutations, those with sensitive gene mutations have the opportunity to use targeted drugs, which can be said to be relatively lucky. Among all lung cancer patients, patients with ALK “diamond mutation” are more fortunate, because compared with other targets and drugs, after oral administration of ALK inhibitors for patients with ALK gene mutations, most patients have significant curative effects, and their condition can be cured. To maintain long-term stability, the survival time is relatively long.
ALK is an anaplastic lymphoma kinase. In 2007, scientists first discovered that there is a gene rearrangement of EML4-ALK with transforming activity in lung cancer. This gene rearrangement can promote the occurrence of lung cancer. and progress. In all non-small cell lung cancers, about 3 to 5% of patients have ALK gene rearrangement positive, and the ALK expression rate of young, non-smoking and EGFR-unmutated lung adenocarcinoma patients can reach 25% to 30%. In the pathological type of mucinous or solid adenocarcinoma containing signet ring cells, the incidence of ALK fusion was higher, reaching 46.2%.
Like EGFR mutation, there are also one, two and three generation drugs for ALK mutation, but they are all foreign original research drugs, the first generation is crizotinib, the second generation alectinib, ceritinib Brigatinib, brigatinib, and third-generation lorlatinib. Among them, the clinical trial data of alectinib is the most dazzling. For newly diagnosed ALK gene fusion patients, the first-line use of alectinib has an effective rate of 92%, significantly prolonging the disease-free survival time of patients by up to 34.8 months.
It is worth celebrating that a domestic ALK inhibitor will be launched in 2020. This drug is Ensatinib, a second-generation ALK inhibitor. Ensatinib is the first and currently the only domestic ALK inhibitor approved for marketing, and it has entered the new version of the medical insurance catalog through medical insurance negotiation. Recently, the drug was approved again for a new indication.
On March 18, the NMPA officially approved the new indication of Betta Pharmaceuticals’ ALK inhibitor ensatinib capsules, which was approved for the first-line treatment of ALK-positive NSCLC. First-line treatment means the first treatment once diagnosed.
Ensatinib was approved for first-line indications based on the data of the international multicenter Phase III clinical study (eXalt3) of first-line treatment of ALK-positive NSCLC patients with ensatinib. As of 2020 On Dec. 8, in the intent-to-treat (ITT) population, median PFS was significantly longer in the ensatinib group than in the crizotinib group (31.3 months vs 12.7 months). The 2-year overall survival (OS rate) rate in the ensatinib group was 78%, also confirming a favorable trend for OS in the ensatinib group. The results of the patients’ quality of life follow-up report showed that the quality of life of the patients in the ensatinib treatment group was significantly improved compared with the patients in the crizotinib treatment group.
Ensatinib and alectinib are compared, and there is no head-to-head clinical study. From the current data, domestic ensatinib is not inferior to alectinib in the first-line treatment of ALK-positive lung cancer patients. Ensatinib showed encouraging improvement in PFS in patients with either first-line or second-line therapy.
In terms of adverse reactions, ensatinib mainly has a relatively high incidence of rash, but relatively mild nausea, vomiting and liver function damage. Overall security is relatively high.