How should ALK and BRAF mutation-positive NSCLC patients choose treatment options?

*It is only for medical professionals to read for reference.
How do ALK+ and BRAF+ patients benefit in the era of precision treatment? Read it in one article! Targeted therapy started the era of precision therapy, and it was non-small cell lung cancer (NSCLC) that has truly entered precision medicine.
Although mutation sites such as ALK and BRAF are rare in NSCLC, they have such a huge population base in China.
Next, there are still not a few patients who benefit from precision treatment.

This time, the medical oncology channel invited Professor Tao Min, the director of the Department of Oncology, the First Affiliated Hospital of Soochow University, Professor Liang Xiaohua, the director of the Department of Oncology, Huashan Hospital, Fudan University, Professor Zhang Liangming, the director of the Department of Oncology, Yantai Yuhuangding Hospital, and the deputy director of the Department of Oncology, Xuzhou Central Hospital.
Professor Han Liang discussed issues related to precise diagnosis and treatment of ALK and BRAF mutation-positive NSCLC patients.

ALK, BRAF and other rare mutations in NSCLC have entered the era of precision medicine.
ALK fusion is relatively rare in NSCLC mutation populations, accounting for only 3 to 5%.
However, ALK-TKI is effective in patients with ALK fusion.
After a reasonable targeted drug treatment, Many patients can survive for 5 years or more, so ALK fusion is also known as the "diamond mutation" of NSCLC.

Professor Tao Min mentioned that “the targets discovered nowadays are relatively rare except for EGFR, but they are indeed developing in a more precise direction.
Although there are only a small number of patients in the population, a target has been discovered.
Further exploration.
The efficacy is indeed better than traditional chemotherapy, and the side effects are significantly reduced.

NSCLC is still exploring more targets, and the discovery of these targets will bring better efficacy to patients.

"BRAF mutations are rarer in NSCLC than ALK fusions.
, Accounting for only less than 2%.
Before the era of targeted drug therapy, there was no precise treatment plan for this part of patients.
Chemotherapy was uniformly used and the efficacy was not optimistic. At present, there are corresponding targeted drugs for NSCLC patients with BRAF V600E mutations.
Professor Liang Xiaohua mentioned, “For NSCLC patients with BRAF mutations, the use of targeted drugs is that the oral administration method brings convenience to the patients.
The curative effect is also much better than the original chemotherapy alone, with fewer side effects.

Therefore, we will recommend that newly diagnosed patients undergo genetic testing, which not only contains EGFR mutation genes, but also rare targets such as ALK and BRAF should also be tested.

" ASCEND-8 clinical research explores new ways of administration.
Asian populations are more suitable for the first-line and second-line indications of NSCLC approved by ceritinib in China, and the approved dose is 450mg/with meals, which is the first approved drug in foreign countries.
The method is obviously different.
In this regard, Professor Han Liang said, “According to the clinical research data of ASCEND-4, Ceritinib was first approved abroad for the 750mg fasting administration method, which is accompanied by its highly effective anti-tumor effect.
It is a significant gastrointestinal adverse reaction, which reduces the compliance of patients with medication.
The
ASCEND-8 clinical study changed the way of taking ceritinib and changed it to 450mg with meals .
The ASCEND-8 clinical study in Asian population was announced last year.
Research data shows that the 3-year PFS rate has exceeded 50%, and the OS rate has exceeded 90%.
This data shows that changes in the way of taking medication improve the efficacy and reduce the adverse reactions caused by the drug.

"What should I do after first-line resistance to ALK-TKIs? ? Individualized diagnosis and treatment is needed for targeted therapy of ALK fusion-positive patients.
The current drugs include the first-generation ALK-TKI crizotinib, the second-generation aletinib, ceritinib, and brigatinib, and the third-generation Laura Tinib, there are even four generations of TPX-0005.

The expansion of the selection range has brought a test for doctors' more refined full-process management.

Targeted therapy will inevitably lead to drug resistance problems after a period of initial treatment.
How patients should choose treatment strategies after the failure of first-line ALK-TKI therapy has also become a major difficulty for targeted therapy of ALK-fusion-positive NSCLC patients.

In this regard, Professor Zhang Liangming believes that after the emergence of drug resistance, the cause of drug resistance must first be clarified.
Generally speaking, there are pharmacological factors and physiological factors. Pharmacological factors: Generally, due to poor compliance of patients, insufficient dosage of medication, or metabolic problems.

In response to such resistance factors, the dosage of the drug can be increased.

If it is a physiological factor, it is recommended that patients undergo second-generation sequencing to further identify the mutant gene.

If the patient is ALK-dependent drug resistance, it should be differentiated according to the patient’s first-line medication, and individualized to replace the new drug for the follow-up treatment plan.
If the patient is ALK-independent drug resistance, bypass activation, etc.
, need to be based on Mutated gene replacement drugs.

How does ALK-TKIs treatment line up? ALK-TKI drugs can significantly prolong the survival of patients, and patients are also at risk of brain metastases.
Therefore, Professor Liang Xiaohua believes, “When choosing drugs, we have to think about which drug will compare the probability of brain metastasis in the future.
Low, secondly, we must consider the issue of drug resistance, and how should the second-line drug be used after first-line resistance.

Thirdly, we must also consider the availability of drugs, and fourthly, toxic and side effects.

" "Seritinib and loratinib Research data shows that they are significantly better than crizotinib in preventing brain metastases, and some patients will develop ALK-dependent drug resistance after crizotinib and ceritinib are administered.
At this time, lauratinib can be used.
Therefore, it is worth considering whether loratinib should be used as the first-line.

"The combination of D+T improves the poor prognosis of BRAF+ patients, a rare target, and the V600E mutation in the BRAF gene with controllable toxicity accounts for more than half, while there are other L956V, G468A , Fusion mutation and other phenomena.

Professor Zhang Liangming said that the V600E mutation type is more common in women and adenocarcinoma, and different mutation types have a greater relationship with the prognosis.

The effective rate of dabrafenib monotherapy in BRAFV600E mutation patients was 33%, but the effective rate of combined first-line and subsequent-line treatment with trametinib reached more than 60%.

 In response to the toxic and side effects of the D+T combination of dabrafenib and trametinib, Professor Liang Xiaohua said that all targeted drugs have some common side effects, such as skin and digestive tract adverse reactions, but Patients generally tolerate it well.

From the experience of using EGFR-TKI, the most important thing is to conduct close observation and follow-up.
If there is a serious adverse reaction, the dose should be reduced or the drug should be stopped in time.
Some patients will tolerate these side effects when the effect is very good.
So gradually developed from level 2 to level 3 or even 4.

In fact, when a serious adverse reaction occurs, stopping the drug for a short time will not significantly affect the efficacy of the drug.

Therefore, close monitoring and measures should be taken during medication to control the occurrence of toxic and side effects while ensuring the efficacy.

How to choose the first-line treatment of BRAF+ melanoma patients with D+T combination? The D+T dual-target therapy program was approved to enter my country, and then it was written into the "CSCO Melanoma Diagnosis and Treatment Guidelines" and was used as the first-line treatment for patients with unresectable BRAF V600E mutant melanoma.
A pair of BRAF inhibitors and MEK inhibitors is recommended.
"Golden Combination" after the first-line treatment is resistant, what should the patient do? Professor Liang Xiaohua believes that it is still necessary to conduct dynamic genetic testing of patients to determine the patient’s drug resistance mechanism.
Follow-up treatment options include targeted therapy and immunotherapy.
From the perspective of the whole process of patient management, it is more inclined to target first and then immunize.
Contribute to the long-term survival benefit of patients.

The previous targeted drug treatment may cost 60,000 to 70,000 yuan a month.
Since targeted drugs have been included in medical insurance, the financial burden of patients has been reduced, and there are more options for follow-up treatment options. Expert profile Tao MinProfessor, First Affiliated Hospital of Soochow University, Chief Clinical Expert, Chief Physician, Doctoral Supervisor, Chinese Society of Clinical Oncology (CSCO) Council Member, Chinese Physician Association, Chinese and Western Integrative Physicians Branch, Oncology Professional Committee Standing Committee Member, Chinese Society of Biomedical Engineering, Cancer Molecular Target Standing member of the Xiang Therapy Professional Committee Standing member of the Non-Small Cell Lung Cancer Expert Committee of the Chinese Society of Clinical Oncology Deputy Chairman of the Oncology Branch of Jiangsu Medical Association Deputy Chairman of the Oncology Committee of Jiangsu Chinese and Western Medical Association Deputy Chairman of the Oncology Committee of Jiangsu Immunology Society Vice Chairman of the Tumor Recurrence and Metastasis Professional Committee of Jiangsu Anti-Cancer Association.
Leader of the Lung Cancer Group, Oncology Branch of Jiangsu Medical Association.
Editorial Board Member of Chinese Journal of Cancer Prevention and Treatment.
Professor Liang Xiaohua, Editorial Board Member of International Oncology Journal.
Tumor, Huashan Hospital Affiliated to Fudan University Department Director, Chief Physician, Doctor of Medicine, Chief of the Oncology Group of the National Drug Clinical Trial Institution, Deputy Director, Department of Oncology, Shanghai Medical College, Fudan University, Chairman, Committee on Cancer Metastasis, China Medical Education Association, Deputy Director, Pelvic Oncology Committee, China Medical Education Association Member, CSCO Neurotumor Expert Committee Member, CSCO Vascular Targeted Therapy Expert Committee Member, CSCO Tumor Support and Rehabilitation Expert Committee Member, Shanghai Anti-Cancer Association Council Member, Shanghai Medical Association Molecular Diagnosis Branch Director, Shanghai Anti-Cancer Association Brain Metastasis Committee Committee Member, Shanghai Anti-Cancer Association Lymphoma Special Committee Deputy Chairman, Shanghai Anti-Cancer Association Difficult Tumor Special Committee Deputy Chairman, Shanghai Anti-Cancer Association Cancer Rehabilitation and Palliative Care Special Committee Standing Committee, Shanghai Anti-Cancer Association Minimally Invasive Tumor Treatment Special Committee Member Professor Zhang Liangming, First Department of Oncology, Chief Physician, Master's Tutor, Yantai Yuhuangding Hospital, Member of the Standing Committee of the Molecular Targeted Therapy Committee of the Chinese Society of Geriatric Oncology, Member of the Interventional Minimally Invasive Professional Committee of the Chinese Society of Medical Education Member of the Lung Cancer Professional Committee of the Minimally Invasive Tumor Committee of the Association Member of the "Minimally Invasive Imaging Diagnosis and Treatment Professional Committee" of the Shandong Medical Imaging Research Association Vice Chairman of the Radioactive Particle Sub-Professional Branch of the Interventional Oncology Branch of the Shandong Medical Doctors Association Microwave Ablation Therapy of the Comprehensive Interventional Branch of the Shandong Medical Imaging Association Deputy Chairman of the Sub-Professional Committee Member of the Standing Committee of the Oncology Branch of the Shandong Medical Doctor Association Member of the Standing Committee of the Chemotherapy Professional Committee of the Shandong Anti-Cancer Association Member of the Standing Committee of the Palliative Care Branch of the Shandong Anti-Cancer Association Member of the Standing Committee of the Lung Cancer Professional Committee of the Shandong Anti-Cancer AssociationProfessor Han Liang, Xuzhou Central Hospital Department of Oncology, Doctor of Medicine, Deputy Chief Physician, Member of the Cancer Rehabilitation Branch of the Chinese Society of Gerontology and Geriatrics, Member of the Cancer Rehabilitation Branch of the Chinese Anti-Cancer AssociationA member of the Translational Medicine Professional Committee of the Chinese Society of Epidemiology presided over two publications from the National Natural Science Foundation of China and published more than ten SCI papers, with a maximum impact factor of 13.
21.
Won a second prize for the introduction of new technologies from the Jiangsu Provincial Health and Family Planning Commission, and a second prize for scientific and technological progress in Xuzhou City One item *This article is only used to provide scientific information to medical professionals, and does not represent the views of this platform