[인터뷰] Park Se-hoon, Professor, Department of Hematology and Oncology, Samsung Hospital Seoul
Professor Park Se-hoon pointed out: “The NTRK gene fusion is only expressed in a very limited number of cases of lung cancer, but since an effective treatment has been developed, active treatment is essential.”
Since 1998, for more than 20 years, lung cancer has ranked first in cancer mortality. Lung cancer is divided into non-small cell cancer and small cell cancer, and about 85-90% of lung cancers are non-small cell lung cancer. Non-small cell lung cancer is caused by various genetic mutations.
In East Asia, including Korea, EGFR mutations are the most common, and KRAS, ALK, and NTRK mutations are also present. Among them, NTRK (neurotrophic receptor tyrosine kinase) gene fusion occurs very rarely, with a frequency of less than 1% in non-small cell lung cancer. The big difference between other carcinomas and cancer caused by NTRK gene fusion is that the tumor has the potential to develop wherever the TRK receptor is located, rather than being limited to specific cells or parts of the body. In other words, the NTRK gene fusion does not discriminate between adults and children. Fortunately, a treatment has been developed for the NTRK gene fusion. It is “Larotrectinib”.
Larotrectinib is a “cancer-specific treatment”. The advantage of cancer-specific anticancer drugs is that they do not require approval for specific treatments. Larotrectinib can be administered when NTRK gene fusion is confirmed. Currently, next-generation sequencing (NGS), fluorescent in situ hybridization (FISH), reverse transcription polymerase chain reaction (RT-PCR), and immunohistochemical staining (Pan-TRK) are currently used as diagnostic methods fusion of the NTRK gene. Among these, the most used test is NGS. If the NTRK gene fusion is discovered in an NGS test, starting treatment immediately is positive for the treatment outcome. We talked about the treatment environment of NTRK with Park Se-hoon, professor of hematology and oncology at Samsung Seoul Hospital.
– Genetic mutations in lung cancer are particularly numerous.
More treatment-applicable mutated genes were found in lung cancer than in those with many mutations. A variety of genetic mutations are found in other types of cancer, but because no drugs have been developed, lung cancer appears to have a particularly high number of genetic mutations.
– Patient survival rates have increased over the past 10 years due to the development of treatments for lung cancer, but it is still the cancer with the highest mortality rate.
It is difficult to say that there is a direct relationship between mutant genes and mortality. However, if a mutated gene is discovered for which a cure is available, personalized treatment can be performed and patient survival rates can be expected to improve.
– Diagnostic technology has also made significant progress.
Right. In the case of lung cancer patients, the types of mutations to be identified are increasing. However, because the use of limited tissue is important, priority is given to testing to identify mutations that can prescribe drugs covered by insurance in line with the reality of our country.
If a mutation is discovered that can use an insurance-covered drug, treatment begins immediately. If the corresponding mutation is not found, further detailed testing is performed. The NGS test is a representative example.
The problem is that there are genes that are difficult to detect with simple tests. It’s the NTRK gene. In this case the NGS test is absolutely necessary. The biggest problem with NGS testing is that it takes about 2 to 3 weeks to get results. I always wonder if it is right to wait for the results and then undergo treatment, or if it is right to start treatment first and then do the test.
– How fast are genetic mutations found in lung cancer?
Among lung cancers, mutations are mainly found in adenocarcinoma. Various types of mutations occur in approximately 60-70% of adenocarcinomas. Among these, the most common genetic mutation is the EGFR mutation. Furthermore, the mutation rate varies depending on gender and smoking status.
– Only a very limited number of NTRK gene fusions are known to be expressed in lung cancer.
It is known to have a frequency of approximately 1% worldwide. I expect it to be similar in Korea, but it’s really rare. However, in the case of the NTRK gene fusion, a drug suitable for the patient has been developed.
– In the case of NTRK fusion lung cancer, are there differences between global and national guidelines?
Same. It is important to discover NTRK gene fusions. The guidelines also state that “larotrectinib” should be used when NTRK gene fusion is confirmed. Fortunately, NGS testing is covered for home adenocarcinoma patients.
– Larotrectinib is the only treatment for NTRK fusion lung cancer.
Larotrectinib is a targeted therapy. The NTRK gene fusion forms a new protein through its machinery. This protein sends signals that allow the cancer to continue growing. This is called an oncogene. Well-known EGFR and ALK mutations also affect tumor cell growth through the same mechanism. Larotrectinib blocks this signal.
– Lung cancer often metastasizes to the brain. The blood brain barrier (BBB) penetration rate of larotrectinib is:
This can be easily observed by looking at the clinical results of larotrectinib. The study included several patients with brain metastases. At this point, the response rate of patients with non-central nervous system metastases that have infiltrated the entire body should be compared with the response rate of brain lesions in patients with central nervous system metastases. Both show similar levels of response rates. Not only in terms of the mechanism of the drug, but also in terms of clinical effects, it seems to pass well across the BBB.
– Differences in prognosis depending on whether larotrectinib is used or not.
Of course there are differences in prognosis. If targeted treatment for the NTRK gene fusion is not performed, patients will only receive cytotoxic anticancer drugs or immunotherapy. Clinical results with larotrectinib show that the response period to treatment is approximately 3 years. Patients using this treatment will be able to control their disease for another three years.
– Is it possible to use larotrectinib in stage 4 lung cancer?
Obviously. Larotrectinib is a drug that is taken continuously. Check once every 2-3 weeks to check for the first side effects. The data shows that patients who respond to larotrectinib have response rates that persist for nearly three years. After confirming the initial response, you can evaluate the response and check for side effects once every 2 to 3 months.
– Receiving the diagnosis of stage 4 lung cancer is emotionally difficult. What lifestyle is recommended for patients?
This is an important question. Among patients diagnosed with stage 4, there have been cases where they did not go out for two or three months. During the Covid-19 period things went even worse. In the case of NTRK gene fusion lung cancer, there are good drugs like larotrectinib, and good targeted treatments have been developed for some other mutations, so it is best to continue living a normal life. Rather, I think overreacting may be worse in terms of overall treatment.
– The biggest problem with targeted cancer drugs is the resistance rate.
According to the research results, the response duration is About 33 months or about 3 years.. Compared to other targeted cancer drugs, larotrectinib is superior.
– Are there cases of lung cancer patients with NTRK gene fusion who are completely cured?
The concept of cure must be approached with caution for terminally ill stage 4 patients. There are cases where clinical data show that patients have achieved complete remission. A complete response means that no tumor is seen on imaging tests. These patients respond very well. It is also important to note how long the response was maintained in patients who showed such a good response. Rather than using the word cure The goal of treatment is to maintain a long period of time without suffering from the disease or without the disease getting worse and without the need for other treatments.
– Precautions when taking larotrectinib.
When the medicine responds well and the body improves, there are people who are not satisfied and think they need to do something more integrative. Representative examples include those using other unproven treatments or folk remedies. Larotrectinib is a safe, long-term drug. However, you have to be very careful because you cannot know what side effects may occur if you combine unproven folk remedies or treatments.
– We also provide multidisciplinary treatment for lung cancer.
Samsung Seoul Hospital provides chemotherapy to lung cancer patients in the hematology and oncology department. The Department of Hematology and Oncology conducts a number of multinational clinical trials and responds quickly to changes in the latest reimbursement or approval standards to provide adequate treatment to patients. The reason we are able to provide adequate treatment to patients like this is because we have great multidisciplinary treatment.
The Department of Hematology and Oncology is affiliated with the Esophageal Lung Cancer Center. If the diagnosis is made by the Department of Thoracic Surgery or the Department of Respiratory Medicine, the Department of Pathology carries out the appropriate investigations. Depending on the results, treatment begins in the hematology/oncology department. When a patient is seen based on the timing of the test, the presence or absence of NGS testing and the timing of treatment are immediately determined to prevent delays in treatment as much as possible.
– Please provide suggestions on how to improve the lung cancer treatment environment.
It is very important to continue treatment without losing hope. I also hope that resistance to clinical trials will decrease. Drugs like larotrectinib were the subject of prospective clinical trials just five years ago. Currently, patients receive standard treatment with this drug. Patients who used larotrectinib 5 years ago were able to use future treatments early because they participated in clinical trials. If there is a good clinical trial and your doctor makes a careful decision based on it, it might be a good opportunity, so please accept it without prejudice.
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