As the "advance force" for precise treatment, the lung cancer field has made breakthroughs in targeted therapy, immunotherapy and other fields. He has published more than 30 SCI papers as a communication/first author, including journals such as Lancet respmed, JCO, JAMA Oncol, PN

*For medical professionals reading only

November of each year is "Lung Cancer Care Month", and November 17 is International Lung Cancer Day, encouraging all sectors of society to improve their accurate understanding of lung cancer. As the "advance force" for precise treatment, the lung cancer field has made breakthroughs in targeted therapy, immunotherapy, and other fields. In recent years, some rare and rare lung cancer driver genes have been gradually "surmounted", and more and more targeted treatment plans have emerged, bringing patients longer survival and better survival benefits. The "medical community" specially invited Cancer Hospital of Chinese Academy of Medical Sciences Professor Wang Zhijie to share with readers the progress of precision treatment of rare targets for lung cancer, and looks forward to the future of targeted treatment of pan-tumor species under the guidance of driver genes.

Expert Profile

Wang Zhijie Professor

Chief Physician

Department of Internal Medicine, Cancer Hospital, Chinese Academy of Medical Sciences

published more than 530 SCI papers with communication/first author (including joint), including Lancet resp med, JCO, JAMA Oncol, PNAS, SciAdvs, Cancer res, Clin Cancer res, JTO and other magazines

was selected as the National "Ten Thousand Talents Plan" Young Top Talents and Beijing Science and Technology Rises.

《Guidelines for the diagnosis and treatment of CSCO Non-small Cell Lung Cancer Written by

Member of the National Anti-tumor Drug Clinical Application Monitoring Committee

Member of the National Tumor Quality Control Expert Committee

Member of the Chinese Clinical Oncology Association (CSCO) Director

Member of the Chinese Clinical Oncology Association (CSCO) Non-small cell lung cancer expert committee Standing Committee

Member of the Chinese Clinical Oncology Association (CSCO) Youth Expert Committee Standing Committee

Member of the Chinese Clinical Oncology Association (CSCO) Young Expert Committee

Member of the Chinese Anti-Cancer Association Lung Cancer Committee

Member of the Chinese Anti-Cancer Association Lung Cancer Committee Deputy Chairman of the Youth Committee of the Association

Member of the Youth Committee of the Chinese Medical Association Tumor Branch

Deputy Chairman of the Chinese Human Health Science and Technology Promotion Association Tumor Chemotherapy Committee

Vice Chairman of the Lung Cancer Committee of the China Elderly Health Association

Member of the Standing Committee of the China Medical Education Association Difficult Tumor Committee

Received the second prize of the National Science and Technology Progress Award (3rd place), the first prize of the Ministry of Education’s “Science and Technology Progress Award for Universities” (2nd place), the first prize of the Chinese Anti-Cancer Association Science and Technology Award (4th place), the eighth Shulan Medical Youth Award, etc.

rare targets for lung cancer have been repeatedly broken through, and accurate detection helps accurately treat

Professor Wang Zhijie: has developed very rapidly in recent years. In addition to targets such as EGFR and ALK, the development of non-small cell lung cancer (NSCLC) drugs under driver gene mutations such as BRAF, KRAS and MET has also gained some results in previous advances. It can be said that targeted therapy based on molecular typing under the guidance of genomics has become a key link in the precise treatment of clinical tumors.

Precision diagnosis is the first step in precise treatment. In the 2022 edition of the "CSCO Non-small Cell Lung Cancer Diagnosis and Treatment Guidelines", it is recommended that patients with advanced NSCLC should not only undergo routine EGFR mutations and ALK fusion detection, but also rare mutations such as BRAF V600E, KRAS, MET 14 exon jump mutations, MET amplification, etc. should be tested. In the selection of test specimens, taking tissue samples for testing is the gold standard, but when tissue samples are not in time, we can also consider using free DNA in the patient's blood circulation for testing, which is also a phased result of the development of accurate detection technology.

is followed by precise diagnosis and precise treatment. In recent years, targeted therapeutic drugs with rare targets have gradually been approved. Taking BRAF V600 as an example, the dual-target regimen of darafenib combined with trametinib achieved positive results in clinical studies and was approved in China for the treatment of advanced NSCLC patients with BRAF V600 mutations in March 2022. Among the clinical research data of registered Chinese in WCLC released this year, the full objective response rate (ORR) of the dual-target regimen reached more than 70%, filling the gap in Asian population data and further confirming the excellent efficacy of darafenib combined with trametinib in patients with BRAF V600 mutations.

In addition, targeted therapeutic drugs targeting MET targets have also made breakthroughs in recent years. The specific MET-TKI has increased the ORR of the advanced NSCLC first-line treatment of this type of driver gene to more than 50% or even close to 70%, and the overall survival period has been increased to 10.9-25.5 months.Therefore, in the NCCN guidelines, specific MET-TKI is listed as the first-line preferred solution for this group of patients. For MET amplification after EGFR-TKI treatment of drug resistance, the EGFR-TKI combined with MET inhibitor regimen has also achieved good results. The ORR can reach about 50%, which makes these secondary drug-resistant patients also have strategies to deal with. The KRAS target, which was previously considered untreated, has also opened a breakthrough in recent years. Since researchers realized the potential of the drug drug of the target KRAS G12C, more and more targeted drugs have emerged. The existing KRAS G12C inhibitors can reach more than 40% for the ORR used in second-tier and later, and the median progression-free survival (PFS) can reach about 7 months, which has good application prospects. There are also some drugs under development that also have huge potential. The data released by the Phase I study show that their ORR can be increased to more than 50%. We also look forward to more evidence-based medicine evidence in the future to bring good news to patients with KRAS G12C mutations.

The treatment strategies for yin and yang are very different. Accurate and accurate

Professor Wang Zhijie: Since entered the era of precise diagnosis and treatment, molecular typing has been a very important link in lung cancer treatment, and the most important step is to judge whether there is a driver gene. Because patients with positive and negative driver genes have different treatment strategies. Patients with positive driver genes generally use targeted therapy, while patients with negative driver genes use immunotherapy and chemotherapy as the main treatment methods.

For NSCLC patients with positive driver genes, including targets such as EGFR, ALK, ROS1, BRAF V600, METex14 jump, KRAS G12C, etc., we already have corresponding targeted treatment plans (some drugs are temporarily out of reach in China), and targeted treatment usually has a higher ORR than traditional chemotherapy, which can reach more than 50%, or even 70%-80%, and the median PFS can reach 7 to 20 months, or even 30 months. Therefore, for patients with positive driver genes, we should undergo molecular typing and then give corresponding targeted treatment.

For NSCLC patients with negative driver genes, chemotherapy and immunotherapy have become key treatment strategies. Usually, it is necessary to test the expression of PD-L1 in the patient's tumor before immunotherapy. If PD-L1 is ≥50%, PD-1 monoclonal antibody or PD-L1 monoclonal antibody monoclonal treatment can usually be selected. Chemotherapy can be combined for specific populations. If PD-L1 is within the range of 1-49%, platinum-containing chemotherapy combined with PD-1 monoclonal antibody is still recommended as the first choice treatment strategy. Of course, if the patient is an elderly person or has a poor basic condition, he may choose to treat immunized monotherapy, and the specific condition shall be based on the individual patient's condition. If PD-L1 expression is negative, the main treatment regimen is based on platinum-containing chemotherapy and selectively combined with antivascular therapy.

targeted treatment of pan tumors, and "treatment of different diseases" may be in the near future. Professor Wang Zhijie: It is entirely possible to open up treatment plans between different cancers driven by the same driver gene in the future. With the deepening of research on driver genes, we will find that a certain driver gene may actually exist in many solid tumors, , and play the same role in driving tumor development in different solid tumors. For example, the BRAF V600 mutation, in addition to NSCLC, is also present in malignant tumors such as thyroid cancer , colorectal cancer, and melanoma. The darafenib combined with trametinib dual-target regimen is currently approved in China in addition to the advanced BRAF V600 mutation-positive NSCLC (BRAF V600 mutation-positive unresectable or metastatic melanoma; postoperative adjuvant treatment of BRAF V600 mutation-positive melanoma). In June this year, the FDA also approved the treatment of BRAF/MEK inhibitors for adults and children over 6 years of age who have progressed after previous treatment or have no other treatment options for BRAF V600E mutations. The approval is based on the results of two studies that include 24 tumor types. The data suggest that the ORR of BRAF/MEK inhibitors can reach 33% to 80% in different solid tumor patients carrying BRAF V600E, which reflects that a certain targeted treatment plan may achieve good therapeutic effects on patients with different solid tumors carrying the same target.

These findings not only exist in BRAF mutations, but also have initially seen similar phenomena in targets such as NTRK and ROS1.I believe that with the development of molecular biology in the future, targeted therapeutic drugs for pan-cancer based on NGS detection may be more applied in clinical practice to achieve the true "two-disease treatment" but the premise is that enough evidence-based medical evidence is needed, and we look forward to clinical research bringing us more evidence.

MCC number TML22111841 valid period 2023-11-21. Expired information will be deemed to be invalid.

*This article is only used to provide scientific information to medical personnel and does not represent the views of this platform