"Doctor, I got the genetic report, but it doesn't contain the targets such as EGFR and ALK that you mentioned earlier. Does that mean I don't have a lot of options?Mr. Zhang asked in frustration. He was diagnosed with advanced non-small cell lung cancer (NSCLC) a few days ago and required a systemic procedure**. As far as he knows, sensitive targets are present to be accurate**, but none of them have been found in his genetic testing report.
Fig. The genetic test report of Mr. Zhang, a lung cancer patient, showed that there was a RET gene fusion.
The doctor looked at Mr. Zhang's genetic test report and said slowly, "Although I didn't carry those common targets, fortunately, the report showed that you carried an abnormality in the RET gene (Figure 1), which means that we can use a targeted drug called a RET inhibitor, such as selpercatinib**." What's more, you can use the most targeted medication for the first round**, which is:First line**
So, why do doctors place so much emphasis on the first line?For lung cancer patients, what is special about the presence of RET targets compared to patients with other targets?
The first line** is essential for the survival of lung cancer patients!
Each cancer patient has only one best chance, and this is the first line, which is decisive for the patient's quality of life.
In the selection of drugs, doctors always follow the principle that first-line drugs are given priority over second-line drugs, and second-line drugs are given priority over third-line drugs. Especially in targeting**, we need to find a target that matches the patient through genetic testing to ensure that the drug can act precisely on the tumor.
If anti-tumor** is compared to a ball game, then second-line and third-line drugs are like substitutes in a ball game. When the first-line ** plan is gradually adapted by the tumor, resulting in poor ** effect, it is necessary to replace the new ** plan, which is like replacing a substitute player who is more energetic and more able to cope with the new changes of the tumor. That's what the second line is all about.
However, no matter how intense the game, the importance of the first team is always irreplaceable. Their performances often dictate the direction of the whole game. Similarly, the choice of first-line ** is also directly related to the quality of life and prognosis of patients. Therefore, doctors will always make the first line of the patient's first priority, and strive to provide the best opportunity for the patient.
For lung cancer patients like Mr. Zhang, who carry RET gene mutations, the importance of first-line ** is self-evident.
The big breakthrough of RET small targets has opened a new door of hope for lung cancer patients
The launch of the RET inhibitor, selpercatinib (LOXO-292), has undoubtedly opened a new door of hope for these patients.
As early as 2012, RET gene fusions were identified as a new oncogene variant in NSCLC patients. This variant is particularly common in young, non-smokers, or lightly smokers with lung adenocarcinoma. Although the incidence of RET gene fusions in patients with non-small cell lung cancer is only 1% to 2%, due to the large patient base in China, the need for precision** for this specific patient population is still very urgent.
On October 8, 2022, a memorable day, the RET inhibitor selpercatinib, a targeted drug specifically targeting RET mutations, was finally approved for marketing in China. Its indications include patients with locally advanced or metastatic RET fusion-positive NSCLC**. The approval of selpercatinib in China is undoubtedly a long-awaited "timely rain" for patients with rare RET targets.
In the latest Libretto-431 study[1], the efficacy of selpercatinib in first-line **RET fusion-positive advanced NSCLC was remarkable. Compared to conventional chemotherapy immunization**, selpercatinib reduced median progression-free survival (PFS) from 112 months to 24In 8 months, it has more than doubled!More importantly, selpercatinib demonstrated excellent intracranial efficacy and efficacy in preventing intracranial progression in the control group.
This means that patients who take selpercatinib do not progress on their tumors for more than two years, which far exceeds the effects of traditional** (chemotherapy, with or without immunization**).
Summary
With the advent of the era of precision medicine, individualization** has become a trend. The development of genetic testing technology allows us to understand the genetic variation of patients more accurately, so as to provide patients with more accurate solutions. Therefore, even if there is no common target in the gene report, like Mr. Zhang, a lung cancer patient in the opening chapter, the hope of ** should not be abandoned. Through genetic testing, other rare genetic variants such as RET may be found, so that the most accurate ** plan can be received.
In short, for those tumor patients with RET gene mutations, RET inhibitors represented by selpercatinib have become a new first-line option, bringing unprecedented hope for survival to patients.
References. 1. h.h.f. loong, k. goto, b.j. solomon, et al. randomized phase iii study of first-line selpercatinib versus chemotherapy and pembrolizumab in ret fusion-positive nsclc. 2023 esmo. lba4.
*:Internet.
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