*For medical professionals only
A number of celebrities gathered in Shanghai to discuss the transformative power of the diagnosis and treatment of rare target NSCLC.
On May 19, 2024, the "2024 China Lung Cancer Rare Target Precision Diagnosis and Treatment Summit Forum" was successfully held in Shanghai. Experts and scholars in the field of lung cancer diagnosis and treatment across the country gathered together to discuss the clinical research progress and treatment strategies of rare targets for non-small cell lung cancer (NSCLC). This conference not only promoted the collision of academic ideas, but also provided a valuable platform for promoting the progress of precision treatment of lung cancer.
Professor Zhou Caicun from the East Hospital of Tongji University, Professor Han Baohui from Shanghai Chest Hospital, Professor Cheng Ying from Jilin Provincial Cancer Hospital, Professor Song Yong from Jinling Hospital affiliated to Nanjing University School of Medicine, and Professor Zhou Xiangdong from Chongqing Southwest Hospital co-chaired the conference. At the beginning of the meeting, Professor Zhou Caicun said that for patients, "519" is a special number, which represents "I want to save", which is the voice and expectation of doctors and patients, and it reminds us to pay attention to and care for these patients. At present, the field of lung cancer treatment has undergone considerable development, and great progress has been made in the field of rare targets of lung cancer, which has prolonged the survival time of patients and improved their quality of life. We look forward to achieving greater achievements in the future and making breakthroughs in the research and treatment of more rare targets."
Professor Zhou Caicun delivered a speech
Professor Cheng Ying said that the study of rare targets in NSCLC has become a hot topic. With the continuous development of a variety of targeted drugs, certain therapeutic effects have been achieved. However, there are still many challenges in the treatment of rare targets in NSCLC, including the rational combination of targeted drugs, the determination of predictors of efficacy, the accurate identification of dominant patient groups, the in-depth understanding of drug resistance mechanisms, and the evaluation of the value of neoadjuvant and adjuvant therapies. It is expected that more innovative targeted drugs will be successfully developed and put into the market, improve the accessibility of treatment for patients, help patients live longer and better, and contribute to the realization of the strategic goal of "Healthy China 2030".
Professor Cheng Ying delivered a speech
Professor Song Yong pointed out that although the rare targets of lung cancer are a small field in the diagnosis and treatment of lung cancer, for China, the population it affects is quite large. We are in an era where we understand and pay attention to rare targets in lung cancer, and we hope that pharmaceutical companies, scientific research scholars and doctors will pay more attention to rare targets.
Professor Song Yong delivered a speech
Professor Zhou Xiangdong shared that the focus of today's discussion is on rare targets, which are not uncommon in China's huge population. The point is that we already have drugs that target these targets. With the development of national pharmaceutical companies in mainland China, especially companies like Innovent Biologics, innovative drugs for lung cancer have shown excellent efficacy.
Professor Zhou Xiangdong delivered a speech
Professor Zhong Hua said that for doctors in the field of lung cancer, they should be committed to providing more practical help and treatment, rather than just staying at the theoretical level.
Professor Zhong Hua delivered a speech
The participating experts jointly kicked off the meeting
Prescient Insight for a New Chapter:
Multi-angle insight into the new progress of rare target mutant NSCLC
Professor Xiong Anwen from the East Hospital of Tongji University gave a detailed introduction to the latest progress in targeted therapy for RET fusion-positive NSCLC at the forum. According to Professor Xiong, the incidence of primary RET fusions in advanced RET fusion-positive NSCLC is about 1.7%, and secondary RET fusions are the most common resistance mechanism after EGFR TKI therapy, accounting for 1.6% of patients with EGFR mutations. Currently, RET inhibitors have been established as the standard first-line treatment option for these patients. The LIBRETTO-431 study, the world's first Phase III randomized controlled study of RET-fusion NSCLC, demonstrated that selpercatinib as a first-line treatment significantly extended progression-free survival (mPFS) to 24.8 months, reducing the risk of disease progression or death by 54% compared with 11.2 months in the control group, thereby reinforcing the standard position of RET inhibitors in first-line therapy. Professor Xiong also mentioned that for patients with oligoprogression after receiving RET inhibitors, continued treatment with selpercatinib can still bring benefits. As for the resistance mechanism of RET inhibitors, only 13% of cases can be attributed to secondary resistance to RET itself, and more than 40% of cases involve bypass activation mechanisms, while most of the resistance mechanisms still need to be further elucidated.
Professor Xiong Anwen
Professor Wang Huijuan from Henan Provincial Cancer Hospital shared the latest progress in targeted therapy for NSCLC ROS1 positive. Professor Wang Huijuan pointed out that although the incidence of ROS1 fusion-positive NSCLC is relatively low, due to the large number of lung cancer patients in mainland China, there is still a huge clinical demand for effective treatment. Especially in the population of patients with brain metastases and after disease progression, there is a lack of effective treatment. At present, a number of new drug studies are being conducted in TKI-naïve and treatment-experienced patients, and preliminary results show good efficacy and safety. In particular, the TRUST-I study showed that tarelitinib demonstrated excellent clinical remission in TKI-naïve, treatment-experienced, brain metastases and drug-resistant patients. As a second-generation ROS1 inhibitor, taralitinib has shown a high response rate in the treatment of ROS1 fusion-positive NSCLC, especially in patients with brain metastases, while bringing a long survival and a good safety profile with a low incidence of adverse reactions in the central nervous system (CNS).
Professor Wang Huijuan
Professor Shi Meiqi from Jiangsu Cancer Hospital shared the latest progress in the treatment of advanced KRAS G12C mutant NSCLC. He said the KRAS mutation is racially different in NSCLC and is more common in Western populations. The incidence of KRAS G12C mutations in Chinese patients is about 3%. Patients with KRAS-mutated NSCLC generally have a poor prognosis, with a median overall survival of about 15 months. For patients with advanced NSCLC with KRAS G12C mutations, the first-line treatment is mainly immune checkpoint inhibitors (ICIs) in combination with chemotherapy, with a mean mPFS of 5 months and a mean overall survival (mOS) of 1 year. However, the options for post-line treatment are relatively limited, and mOS is only half a year. Therefore, there is a large unmet clinical need for patients with advanced NSCLC with KRAS G12C mutations. In the Phase I/II clinical study, fluzerexib (a KRAS G12C inhibitor) was shown to achieve rapid and durable remission in patients with advanced NSCLC with KRAS G12C mutations, with a favorable overall safety profile. The advent of KRAS G12C inhibitors has provided new treatment options for these patients. In order to further explore the clinical benefits of KRAS G12C inhibitors, a variety of combination therapy regimens are currently being actively explored, in order to provide more effective treatment strategies for patients with advanced NSCLC with KRAS G12C mutations.
Professor Shi Meiqi
The discussion session of "Foresight, New Chapter of Insight" was chaired by Professor Zhou Caicun, and Professor Chu Tianqing from the Chest Hospital of Shanghai Jiao Tong University School of Medicine, Professor Fan Min from the Cancer Hospital of Fudan University, and Professor Tang Kejing from the First Affiliated Hospital of Sun Yat-sen University respectively expressed their views on the diagnosis and treatment and current development of rare mutant targets.
Professor Chu Tianqing said that the current challenges in the diagnosis and treatment of rare targets in lung cancer mainly lie in the acquisition of samples. It is hoped that the detection platform can be optimized to accurately test samples in the case of limited resources. As drug selectivity increases, experience gains, and patient treatment strategies continue to evolve, existing testing platforms need to adapt to these changes. "While there are other issues to consider, such as cost, I believe that the optimization of the inspection platform is the most pressing need right now."
Professor Tang Kejing shared that in the diagnosis of lung cancer, the inadequacy of detection methods such as immunohistochemistry may limit the identification of rare targets. "In addition to the known targets in NSCLC, there are many less common targets that deserve attention. In clinical practice, we have found that lung cancer patients with FGFR fusions are indeed effective after the use of pemitinib. This suggests that we need to study more potential targets and accumulate clinical data in the future in order to obtain more new drug treatment indications for lung cancer patients. ”
Professor Fan Min said that in the treatment of rare targets for lung cancer, although the current drugs have achieved certain efficacy, we still need to seek more effective treatment options. This includes considering whether combination therapies can be used to improve efficacy, and how to advance drugs that are currently primarily used for post-line therapy to more front-line treatments.
Prof. Zhou Caicun, Prof. Chu Tianqing, Prof. Fan Min and Prof. Tang Kejing participated in the discussion session (scroll up and down)
The target grip is accurate, and Daze is reborn:
Rare target detection takes precedence, leading a new journey of precision medicine
Professor Xiaoyan Zhou from the Department of Pathology, Fudan University Cancer Hospital, made a detailed analysis of three rare targets, RET, MET 14 skipping mutation and KRAS G12C, and pointed out the problems encountered in clinical diagnosis and treatment. She emphasized that single-gene testing is not recommended for testing due to the wide variety and low incidence of rare targets in NSCLC. Instead, a multi-gene parallel assay approach should be employed, and the coverage of the assay reagents should be known. Professor Zhou also mentioned that the establishment of a multi-platform detection system is the development trend of precision medicine. With the widespread use of next-generation sequencing (NGS) technology, there is a need to validate the assay results of each platform to ensure the accuracy of the results. When the detection results of different platforms are inconsistent, the cause should be analyzed in a timely manner and multi-platform verification should be carried out. When optimizing the detection strategy, it is important to take into account the timeliness and the number of targeted genes. After assessing the quality of the specimens available for testing and the applicable testing methods, the patient's visit time and disease progression need to be comprehensively considered. For patients who are initially tested and retested, an appropriate testing strategy should be selected to provide maximum clinical assistance.
Professor Zhou Xiaoyan
Professor Chen Yuqing from the First Affiliated Hospital of Bengbu Medical College, Professor Shi Jian from the Fourth Hospital of Hebei Medical University, and Professor Zhou Jianya from the First Affiliated Hospital of Zhejiang University School of Medicine participated in the discussion and expressed their views.
During the discussion, Professor Chen Yuqing emphasized the importance of testing in the diagnosis and treatment of lung cancer. She mentioned that the prerequisite for obtaining a target is to obtain high-quality specimens. Special mention was made of respiratory endoscopy techniques, including general tracheoscopy, fluorescence tracheoscopy, and endoscopic ultrasound navigation systems, which can help us obtain specimens from small lung lesions and are essential for accurate detection. She also noted that pleural effusions or blood may also be viable samples if tissue specimens are not available. The variety of detection methods provides a guarantee to ensure the accuracy of the detection.
During the discussion, Professor Shi Jian emphasized the importance of testing first, and although the concept of genetic testing has been deeply rooted in the hearts of the people, there are still challenges in the implementation process. For example, when collecting specimens, it is necessary to consider the choice of primary or metastatic lesions, as well as specimens from different metastatic sites. Professor Shi suggested that among metastatic lesions, priority should be given to blood-rich sites such as liver metastases, which may have more variations. At the management level, Professor Shi mentioned that as the director of the Hebei Provincial Medical Oncology Management Center, she is promoting multidisciplinary collaboration, especially the combination of pathology and clinical practice. She advocated for the establishment of pathology databases to facilitate information sharing and academic research among different hospitals and specialties.
Professor Zhou Jianya pointed out that clinicians should pay more attention to testing and diagnosis and treatment strategies to improve their professional level. She illustrates this with the case of a drug-resistant patient who was started on chemotherapy in combination with anti-angiogenic therapy after a re-biopsy of a lung lesion found no meaningful target. During treatment, the lung lesions shrink, but the adrenal lesions enlarge. The patient underwent a second biopsy and immunohistochemistry showed a strong positive (+++) MET test, which responded to chemotherapy combined with a MET inhibitor. This case highlights the importance of repeat biopsies in specific situations and the positive outcomes that immunohistochemistry can bring when PCR or NGS methods fail to achieve their goals.
Prof. Xiangdong Zhou, Prof. Yuqing Chen, Prof. Jian Shi and Prof. Jianya Zhou participated in the discussion session (scroll up and down)
In the summary of the conference, Professor Han Baohui pointed out that after in-depth thematic discussions and expert interactions, we have a deeper understanding of the diagnosis and treatment of rare targets in lung cancer in China. He mentioned that despite the great efforts of clinicians and pharmaceutical companies, some policies have not yet been implemented, such as NGS testing has not been standardized in China. In order to solve this problem, it is necessary to promote the relevant management departments through industry association meetings and expert interpretations. Although rare targets are rare but not rare, we need to identify them through precise diagnosis and bring survival benefits to patients through precision therapy.
Professor Han summarized the conference
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