With the launch of the “Precision Diagnosis and Treatment of Rare Targets of Lung Cancer” project, it will comprehensively promote the standardization of diagnosis and treatment of rare targets of lung cancer in my country, thereby benefiting more patients.
China has a huge base of lung cancer patients, and the clinical needs of patients with rare gene mutations in lung cancer cannot be ignored. With the discovery of more and more rare targets of lung cancer and corresponding targeted therapy drugs, patients with advanced non-small cell lung cancer (NSCLC) have more options for treatment, and more precise and individualized diagnosis and treatment strategies for NSCLC are proposed. requirements.
On September 4, 2022, the launch meeting of the “Precision Diagnosis and Treatment of Rare Targets in Lung Cancer” project was held. The project is jointly launched by the Chinese Society of Clinical Oncology (CSCO) Non-Small Cell Lung Cancer Special Committee and the China Medical Education Association, two authoritative organizations. It is planned to be launched nationwide from September to December 2022. The cooperative hospital established a precision diagnosis and treatment center for rare targets of lung cancer, and established a regional rare target diagnosis and treatment alliance with this hospital as the core, so as to accumulate and promote the diagnosis and treatment experience of rare targets of lung cancer, and jointly promote the improvement of the level of lung cancer diagnosis and treatment in China.
The conference was chaired by Professor Zhou Caicun of Shanghai Pulmonary Hospital Affiliated to Tongji University and Professor Ying Jianming of Cancer Hospital, Chinese Academy of Medical Sciences .
Professor Zhou Caicun said in his speech: “In recent years, the diagnosis and treatment of rare/rare targets for lung cancer has made great progress, and many targets are already available in clinical practice. However, at present, clinicians still have insufficient knowledge of rare targets, and there are still great difficulties in how to do accurate detection, how to manage the whole process, and how to use targeted therapy to the extreme. Awareness of targets and academic exchanges are very important. Only by raising awareness and doing accurate detection and treatment can the prognosis of patients be improved. Moreover, although rare targets are rare, due to the huge population of lung cancer in my country, the overall number is not large. This conference brings together multidisciplinary experts such as medical oncology, respiratory, surgery, molecular pathologists, etc., which will promote the improvement of rare target diagnosis and treatment.”
Professor Zhou Caicun
Professor Ying Jianming delivered a speech from the perspective of pathology experts, he pointed out: “TKI drugs have become an important means of lung cancer treatment, and accurate detection of rare Targets require certain technologies, methods, processes, etc., especially the communication between the pathology department and the clinical department is very important. Only in this way can patients with advanced lung cancer be able to accurately detect rare target mutations and obtain effective TKI drugs treatment.”
Professor Ying Jianming
Ms. Yan Wei, Head of the Oncology Division of Takeda China said in her speech: “In March this year, brigatinib was approved by the State Drug Administration for For the treatment of patients with locally advanced or metastatic ALK fusion-positive non-small cell lung cancer, it brings new options and hope to the domestic patient population. Coincidentally, on July 12, 2021, the National Medical Products Administration (NMPA) drug review The Center (CDE) officially accepted the Marketing Authorization Application (NDA) of Mobocertinib (TAK-788), a first-class innovative drug in the lung cancer field submitted by Takeda Pharmaceutical, and was approved to be included in the priority review and approval process. This drug is expected to become the first domestic drug to overcome EGFR ex20ins. A targeted therapy drug. Takeda China officially entered the field of lung cancer, and joined hands with experts to contribute to the benefit of many rare target lung cancer patients! Takeda is very honored to join the team that promotes the development of clinical diagnosis and treatment of rare targets in lung cancer. Participate in the ‘Precision Diagnosis and Treatment Project of Rare Targets of Lung Cancer’, provide a favorable weapon for the clinical treatment of rare targets of lung cancer, and promote the standardization from disease recognition to diagnosis and treatment. Accumulate more advanced clinical diagnosis and treatment experience in China and share it with clinical clinics around the world doctors and more patients.”
Ms. Yan Wei
After the wonderful speeches, all the guests jointly launched the “Precision Diagnosis and Treatment of Rare Targets of Lung Cancer” project to help improve the level of precision diagnosis and treatment of rare targets of lung cancer in China.
Precision diagnosis, testing first
Then the conference entered the academic session, the first chapter “Precision Diagnosis and Testing First”Co-chaired by Professor Zhou Caicun and Professor Ying Jianming.
Professor Meng Bin from Tianjin Medical University Cancer Hospital shared the theme report of “Precision Detection Strategy of Lung Cancer under the Guidance of Companion Diagnostics”. Professor Meng introduced the detection methods, detection procedures and related guidelines/consensus recommendations of ALK, EGFR ex20ins, MET and RET in detail, and elaborated the optimization strategy for the overall detection of lung cancer. Taking ALK as an example, the main detection methods include immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), real-time quantitative polymerase chain reaction (RT-PCR) and next-generation sequencing (NGS). Among them, IHC has the advantages of economy, rapidity, and simple operation, and it is recommended to be used first; when it is detected together with other genes (such as EGFR, ROS1, etc.), it can be combined with FISH and RT-PCR, or RT-PCR or NGS multi-gene detection, In this way, samples and testing time can be saved; when quality problems are suspected in testing samples, FISH testing is given priority; in addition, priority testing items and testing methods can be selected based on clinical pathological characteristics.
Professor Meng also introduced the current models of pathology and molecular pathology testing, and pointed out that the “patient, pathology department + laboratory, clinician” model has more advantages, such as more accurate molecular diagnosis , The cycle is shorter, and the molecular diagnosis results can be integrated into the pathology report, providing clinicians with clear mutation sites and meanings, and facilitating communication between clinicians and pathologists.
Finally, Professor Meng concluded that the diagnosis and treatment of lung cancer has entered the era of “precision medicine”, and pathological diagnosis and detection run through the entire process of diagnosis and treatment of lung cancer. With the increase in lung cancer target molecule detection items and the increase in the types of test samples, which detection platform and process should be used should consider a variety of factors. In the era of precision treatment, the role of companion diagnostics for lung cancer has become indispensable.
Professor Meng Bin
In the following sessions, Professor Chu Qian of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Professor Fan Yun of Cancer Hospital Affiliated to University of Chinese Academy of Sciences, Zhejiang University School of Medicine Professor Zhou Jianying from the First Affiliated Hospital had a lively discussion on “the best detection strategy and route for advanced lung cancer patients” and “how molecular detection can guide the treatment of drug-resistant patients with advanced driver gene-positive NSCLC”.
Professor Chu Qian pointed out that at present, almost all clinically diagnosed NSCLC patients will receive genetic testing, and the testing methods will vary depending on the patient’s economic ability. different. In general, oncologists have very strong detection awareness and standardized detection strategies. However, the detection path still needs to be further improved, and the “closed loop of detection composed of patients, clinicians and pathologists” proposed by Professor Meng will become the mainstream in the future.
Professor Fan Yun said that NGS is widely used in clinical practice due to its advantages of comprehensive detection. While DNA-based NGS may miss detection for gene fusions, adding RNA-based NGS essentially circumvents this problem. In addition, she hopes that pathologists can further strengthen the quality control and training of molecular testing to make the testing results more accurate.
Professor Zhou Jianying said that in the era of precision medicine, the pathology department plays an important role in the diagnosis and treatment of lung cancer. For first-diagnosed lung cancer patients, their hospitals usually do 9 gene tests, covering most of the drug-available targets; for those with drug resistance, a second biopsy will be performed to guide follow-up treatment. At present, there are new targets, new drugs, and new technologies for the diagnosis and treatment of lung cancer. Through the launch of the “Precision Diagnosis and Treatment of Rare Targets of Lung Cancer” project, cooperation between different hospitals will be promoted, which will further promote the accurate diagnosis and treatment of lung cancer.
Professor Zhou Caicun concluded that genetic testing should be carried out throughout the entire treatment process, including baseline, during treatment, and after drug resistance. To do a good job in genetic testing, firstly, clinicians should obtain appropriate specimens, secondly, pathologists should select the appropriate testing platform, and finally, the testing method should be selected according to the patient’s economic ability. Clinicians and pathologists should communicate, communicate and cooperate well.
The Daoist Talk: Prof. Zhou Caicun, Prof. Fan Yun, Prof. Zhou Jianying and Prof. Chu Qian
Precision diagnosis and treatment, standardization progress
The second chapter, “Precision Diagnosis and Standardization Advancement”, is led by Professor Han Baohui from the Chest Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Professor Lu Yu from West China Hospital, Sichuan University Host.
Prof. Fang Wenfeng, Prof. Wang Jialei and Prof. Lu U
Professor Fang Wenfeng from Sun Yat-Sen University Cancer Center brought a keynote report on “Focus Guidelines-Targeting Rare Target Treatment Specifications for Lung Cancer”. Professor Fang pointed out that although the survival of patients with common target mutations in lung cancer in my country has been significantly prolonged, the survival of patients with rare target mutations is worrying, and there are still many unmet needs. Fortunately, in recent years, targeted therapy has made great progress, and many rare targets are already available. For ALK integration, domestic ALK-TKIs have already presented a “three generations in the same house”Among them, second-generation ALK-TKIs such as brigatinib have become the new standard of first-line treatment; ROS1, MET ex14, BRAF V600E, RET and NTRK have been approved in China; the corresponding target drugs of EGFR ex20ins and HER2 are temporarily in China. Not approved, but the U.S. Food and Drug Administration (FDA) has approved corresponding drugs, and CSCO guidelines have made corresponding recommendations. For example, moboxitinib and Amivantamab are recommended for the later-line treatment of EGFR ex20ins NSCLC.
Finally, Professor Fang Wenfeng concluded that in the field of lung cancer, whether it is a classic EGFR mutation or a rare/rare target, as long as it is really defined as a driver gene, No matter how complicated and arduous the research and development process is, we will eventually see the emergence of a “magic drug” with very good curative effect. However, among these approved new drugs, the contributions made by Chinese companies and Chinese scholars are still limited. In the future, it is hoped that the two sides can strengthen cooperation and make more Chinese contributions.
Professor Fang Wenfeng
Professor Wang Jialei from Fudan University Affiliated Cancer Hospital brought a keynote report on “The New Pattern of First-Line Treatment of ALK Positive Advanced NSCLC”. Professor Wang pointed out that controlling tumor progression and prolonging survival is an important goal of first-line treatment of ALK-positive advanced NSCLC. In clinical practice, the choice of first-line treatment should aim at maximizing clinical benefit, and consider multiple factors:
Stronger disease control: The new generation of ALK-TKIs further improved the survival benefit in the overall population. Brigatinib has a high remission rate and durable remission duration, and the proportion of patients with deep remission is 56%, which helps to improve the benefit of progression-free survival (PFS)/overall survival (OS).
Broader population benefit: ALK-TKIs should broadly cover the general population and Asian populations, and brigatinib may provide greater survival benefit in different populations.
Longer survival time: The new generation of ALK-TKIs has improved control of intracranial lesions. Brigatinib can bring high PFS and OS benefits to the baseline brain metastases population, and there are still options for later-line treatment after progression.
Better quality of life: Brigatinib has a good safety profile and is well tolerated with long-term use. It is the first ALK-TKI to achieve significant survival and quality of life benefits.
In addition, in order to further improve the long-term survival of patients with ALK-positive NSCLC, the current multi-level exploration of new directions, new drugs, new programs and new strategies is continuing.
Professor Wang Jialei
In the Dao discussion session, Professor Dong Xiaorong of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology and Professor Yu Zhuang, Affiliated Hospital of Qingdao University School of Medicine /strong>She delivered wonderful academic views on the topics of “How to Promote the Standardized Treatment of Rare Targets in Lung Cancer” and “The Most Concerned ALK-TKI-related Data and Clinical Guidance for First-Line Treatment of ALK-positive Advanced NSCLC Patients”.
In response to the first topic, Professor Dong Xiaorong said that in order to achieve standardized treatment of rare targets in lung cancer, we need to start from the following two points: First, we must first discover Rare targets, therefore, patients with lung cancer, especially adenocarcinoma, should carry out adequate genetic testing and strictly control the quality; All should be included in the database for unified management and observation, so as to further understand the efficacy and safety of drugs.
Professor Yu Zhuang introduced that the pathologist of his hospital conducted statistics on 38 hospitals in Qingdao and found that about 1/3 of the hospitals carried out ALK testing relatively standard. In addition, statistics from the Jiaodong area found that the positive rate of ALK was only 3.3%, which is a certain gap compared with the previously thought of 5% to 6%. This may be related to the fact that many patients did not find ALK mutations in the early pathological tests. In this regard, they have established a pathological diagnosis alliance in Jiaodong region composed of experts in pathology, radiotherapy and medical oncology. treatment, and promote standardized treatment.
Professor Han Baohui further affirmed the importance of standardized and precise diagnosis for precise treatment of rare targets, and pointed out that rare target mutations are not only seen in newly treated patients, and can occur after resistance. At the same time, Professor Han Baohui also emphasized that in clinical practice, an individualized treatment plan should be formulated according to the specific situation of the patient, including family status, degree of cooperation, and comorbidities.
In response to the second topic, Professor Dong Xiaorong pointed out that the first-generation ALK-TKI has certain limitations, including that the effect on brain metastasis needs to be improved, and the PFS of first-line treatment has been improved. However, the second-generation ALK-TKI basically overcomes these limitations. Among them, brigatinib has two data that have attracted more attention. One is that it can bring complete remission (CR) to 1/4 of patients, which is rare; the other is that it can improve the quality of life. On the ALK pathway, if a drug has a longer PFS, a good effect on brain metastases, and a significant improvement in quality of life, it is a better choice for ALK-positive patients.
Professor Yu Zhuang said that brigatinib has multiple advantages: the PFS of first-line treatment is about 31 months, the PFS of patients with brain metastases at baseline is about 24 months, The 4-year OS rate was 71%. Clinical drug selection mainly considers efficacy, safety and economy. In the future, it is hoped that brigatinib can enter medical insurance as soon as possible, so that more patients can benefit from it.
Professor Han Baohui concluded that allowing patients to liveTo live long, live well, live comfortably, and live with dignity is the goal of current medical care. To achieve this goal, clinical attention may be paid to the depth of treatment remission, that is, the CR rate. The higher the proportion of patients who achieve a CR rate in the first-line treatment, the stronger the depth of remission, the lower the probability of drug resistance, and the longer the PFS and even OS. Deep remission may be an important marker for predicting efficacy, representing the intensity of reduced tumor burden and reduced tumor activity. It has been previously observed in other tumor types that the higher the proportion of pathological CR or clinical CR, the better the PFS, and the higher the proportion that translates into prolonged OS.
Daoist Talk: Prof. Han Baohui, Prof. Yu Zhuang and Prof. Dong Xiaorong
Precision diagnosis and treatment targeting the future
Chapter 3 “Precision Diagnosis and Treatment Targeting the Future” is served by Professor Wang Zhehai from Shandong Cancer Hospital and Professor Zhang Lanjun from Sun Yat-sen University Cancer Center host.
Professor Zhang Lanjun
Professor Huang Meijuan from West China Hospital of Sichuan University shared “The Shining Stars-2022 WCLC Rare Targets of Lung Cancer New Progress”. For KRAS G12C mutant NSCLC, more explorations have been made on the combination therapy of Sotorasib, and GDC-6036 and D-1553 single drugs have also shown initial efficacy. For rare EGFR mutations, NGS is superior to PCR in identifying clinically significant driver mutations. Real-world data on EGFR ex20ins with moboccetinib (median OS 22.4 months) and amivantamab (ORR 30%) and later-line suvatinib (ORR 52.4%) are also available in 2022 Announced at WCLC.
In addition, many breakthroughs have been made in driver gene mutation targets such as ROS1 fusion, BRAF V600R mutation, NTRK fusion, MET ex14 skip mutation, and RET fusion. The latest data show that the median PFS of entrectinib in the treatment of ROS1-mutant NSCLC was 16.8 months and the median OS was 44.1 months; the ORR of dabrafenib combined with trametinib in Chinese patients with BRAF V600E-mutant NSCLC reached 75 %, the 6-month OS rate was 100%; larottinib treatment of NTRK fusion lung cancer had OS of 40.7 months; Capmatinib treatment of MET ex14 skipping mutation had a real-world median OS of 18.2 months, and Tepotinib validation cohort data showed that ORR was 54.7 %, median OS was 18.8 months; TA0953/HM06 showed antitumor activity in the treatment of RET mutations.
Professor Huang Meijuan
In the discussion session, Professor Ma Zhiyong from Henan Cancer Hospital, Professor Shen Bo from Jiangsu Cancer Hospital, and Professor Yao Yu from the First Affiliated Hospital of Xi’an Jiaotong University Focused on “2022 WCLC rare target treatment progress of lung cancer and its guidance and impact on clinical practice” and “how to promote the accumulation of real-world data on rare targets in lung cancer”, heated discussions were held.
Professor Ma Zhiyong pays more attention to the progress of KRAS G12C and EGFR ex20ins mutations, because they account for a large proportion of rare targets. At present, the main research results of these two targets focus on the treatment after the second line. In the future, it is hoped that these drugs can be further studied with a larger sample size or head-to-head, so that the treatment can be moved to the first line.
Professor Shen Bo pays more attention to rare targets for which drugs are available or will soon be available, and points out that the effective rate of last-line treatment reaches 30%~ Studies with 50% or PFS over 10 months were very clinically meaningful. Although some drugs are currently recommended as level II or III in the guidelines, with the approval of the China Food and Drug Administration, including the official release of domestic phase II clinical research data, they will soon become level I recommendations for the diagnosis and treatment of lung cancer. Bring strong guiding significance.
Professor Yao Yu pointed out that in addition to KRAS G12C and EGFR ex20ins mutations, she also pays attention to the HER2 target, and hopes that DS-8201 will be approved for marketing in China as soon as possible. The research carried out by Professor Han Yuchen divided the MET ex14 skipping mutation into 4 pathological subtypes, which may make the treatment population more precise in the future.
As for how to promote the accumulation of real-world data on rare targets of lung cancer, the three experts agreed that on the one hand, clinical attention should be paid to the collection of data on rare targets in the past, and on the other hand, the grass-roots level should be strengthened The improvement of the hospital’s understanding of rare targets and the level of diagnosis and treatment has enabled patients with rare target mutations to receive standardized diagnosis and treatment at the grassroots level. At the same time, by establishing a unified platform, real-world data can be better accumulated.
Professor Wang Zhehai concluded that with the continuous improvement of genetic diagnosis technology, the accumulation of clinical research data, and the improvement of drug availability, the diagnosis and treatment of rare targets in lung cancer will be better Into routine clinical practice, the audience will be wider, and some real-world problems will be solved and improved.
Daoist Talk: Prof. Ma Zhiyong, Prof. Yao Yu, Prof. Wang Zhehai and Prof. Shen Bo
At the end of the meeting, Professor Zhou Caicun summarized the meeting and pointed out: “For rare/rare targets, we need to raise awareness and increase the detection rate. It is hoped that we can catch all patients with rare/rare target mutations clinically, and then give precise treatment. This is our best treatment strategy. Of course, there are still many problems in clinical research, such as rare target drug resistance. What is the mechanism? How to overcome drug resistance? What is the efficacy and safety of rare target drugs in the Chinese population? All these need to be answered by the joint efforts of clinical experts.
Chinese lung cancer experts are very professional and skilled, with strong clinical diagnosis and treatment capabilities, a large number of patients, and a good level of translational research. As long as everyone unites together, we will be able to achieve rare targets in the future. have the right to speak. I have always thought that rare/rare targets should be a gift from God to our Chinese experts. The key is that we must act.
Finally, thanks to Takeda’s support, Takeda already has very good rare target drugs, including brigatinib and mobsitinib, and I hope these products will play a better role in clinical practice. increasingly important role. “
Professor Zhou Caicun
More than 7,000 people watched the launch meeting of the “Precision Diagnosis and Treatment of Rare Targets of Lung Cancer” project. In the future, the project will hold more series of conferences to build an academic exchange platform for the diagnosis and treatment of rare targets of lung cancer. And promote the diagnosis and treatment experience of rare targets of lung cancer, jointly help improve the level of precision diagnosis and treatment of rare targets of lung cancer, and then benefit more patients. We sincerely invite you to continue to pay attention!
Proofreading: Zang Hengjia
Editor in charge: Song Kunlun
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