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Targeted, immune, and new drugs have shown their talents, bringing hope to patients with advanced lung cancer.
On April 20, 2024, the North-South Conference on the Frontier and New Development of Lung Cancer was held in Changchun. This conference brings together the top experts and the latest scientific research achievements in the field of lung cancer in China, aiming to promote the exchange of cutting-edge lung cancer scientific research and promote the progress of lung cancer diagnosis and treatment technology.
The conference invited Professor Cheng Ying from Jilin Provincial Cancer Hospital, Professor Fan Yun from the Cancer Hospital Affiliated to the University of Chinese Academy of Sciences, Professor Han Baohui from the Chest Hospital Affiliated to Shanghai Jiao Tong University, Professor Huang Cheng from Fujian Provincial Cancer Hospital, Professor Ma Zhiyong from Henan Cancer Hospital, Professor Yu Yan from the Cancer Hospital Affiliated to Harbin Medical University, and Professor Zhao Mingfang from the First Affiliated Hospital of China Medical University to serve as the chairmen of the conference. In the opening session, Prof. Cheng Ying and Prof. Han Baohui, chairs of the conference, said in their opening remarks that the conference focused on a number of hot topics such as driver gene-positive advanced non-small cell lung cancer (NSCLC), driver-negative advanced NSCLC, stage III NSCLC, and small cell lung cancer (SCLC) treatment strategies, and shared evidence-based medical evidence in the fields of targeted therapy and immunotherapy, in anticipation of colliding with new sparks of thinking and contributing to improving the long-term survival of lung cancer patients in mainland China.
Figure 1. Professor Cheng Ying delivered an opening speech
Figure 2. Professor Han Baohui gave an opening speech
Witnessed by the guests of the presidium and many experts on the scene, the launching ceremony of the CSCO Young Lung Cancer Debate Competition was officially unveiled.
Figure 3. The launching ceremony of the CSCO Young Lung Cancer Debate Competition
Chapter 1 - "Targeting" the future
■ Feel the addition and subtraction of lung cancer treatment
Under the chairmanship of Professor Fan Yun and Professor Ma Zhiyong, the chairman of the conference, the conference entered the first chapter.
Figure 4. Professor Fan Yun presided over the meeting
Figure 5. Professor Ma Zhiyong presided over the meeting
Professor Zhang Linlin from Tianjin Medical University General Hospital shared the innovation of first-line treatment strategies for lung cancer in the era of precision therapy.
Figure 6. Professor Zhang Linlin's academic report
Both the FLAURA2 and MARIPOSA studies demonstrated a significant benefit in the osimertinib combination arm compared with the osimertinib monotherapy arm, with the FLAURA2 median progression-free survival (PFS) significantly longer than that in the monotherapy group of approximately 9 months, the median PFS was 11 months longer than that in the monotherapy group in patients with central nervous system (CNS) metastases at baseline, and the CNS CR rate reached 59%; In patients with positive L858R mutations, median PFS was 11 months longer than in the monotherapy group. First-line combination therapy based on third-generation EGFR-tyrosine kinase inhibitors (TKIs) is breaking through the boundaries of single-agent efficacy and reshaping the first-line treatment landscape.
The first-line targeted therapy mode of NSCLC with positive other driver genes (such as MET, ROS1, KRAS, etc.) is being explored, which is expected to change the first-line treatment landscape in the future. With the development of precise staging and molecular pathology detection of lung cancer, and the exploration of new models such as bispecific antibodies, cell therapy, and electric field therapy, NSCLC has entered the era of precision treatment.
■ Listen to real-world sounds
Professor Tang Kejing from the First Affiliated Hospital of Sun Yat-sen University interpreted the real-world evidence of EGFR mutation-positive patients with advanced NSCLC in China.
Figure 7. Professor Tang Kejing's academic report
Compared with the FLAURA study, three real-world studies in China (FLOURISH, Prof. Wang Mengzhao, and Prof. Lu Shun) were 100% included The results suggest that in the first-line treatment of Chinese patients with EGFR mutation-positive advanced NSCLC, osimertinib in the first-line treatment of Chinese patients with EGFR mutation-positive advanced NSCLC has been consistent with or even better results than the FLAURA study, with a median PFS of up to 23.5 months. Osimertinib is being explored in a larger population, including patients with EGFR mutation-positive stage III unresectable disease, patients with EGFR rare mutation-positive mutations, elderly patients, and patients with dose down-regulation due to adverse events (AEs).
■ Discussion session
Under the chairmanship of Professor Chen Jun from the Second Affiliated Hospital of Dalian Medical University, Professor Liu Jingjing from Jilin Provincial Cancer Hospital, Professor Li Yan from the Affiliated Cancer Hospital of Shandong First Medical University, Professor Zhang Jiaxing from the First Affiliated Hospital of Sun Yat-sen University, and Professor Liu Yanling from Jilin Provincial Cancer Hospital discussed the hot topics of diagnosis and treatment of EGFR mutant NSCLC and beneficiary groups.
Figure 8. Panelists
Prof. Jingjing Liu: The most impressive thing in FLAURA2 study is the combination therapy of patients with brain metastases, and the high complete response rate (CR) really helps patients achieve maximum tumor remission and improve survival rate.
Prof. Yan Li: FLAURA2 the trend of positive overall survival (OS) results in the study is very obvious, and from the current study, people with refractory TP53 co-mutations and L858R mutations will benefit more. Therefore, it may be necessary to conduct a screening of the population in the clinic.
Professor Zhang Jiaxing: Lung cancer treatment focuses on precision, and most lung cancer patients who are clinically contacted resist chemotherapy and usually choose a personalized treatment plan based on the patient's test results and physical condition.
Prof. Yanling Liu: In FLAURA2 studies, clinicians are most concerned about the trend of OS benefit. The World Lung Cancer Congress in March this year announced a clear trend of OS benefit from the FLAURA2 study, and PFS was also significantly better than that of the control group. Osimertinib + chemotherapy may be of greater benefit in patients with brain metastases and L858R mutations.
Chapter 2 - "Immunity" is king
■ Looking forward to the future of phase III immunotherapy
Under the chairmanship of Professor Yu Yan and Professor Zhao Mingfang, the conference entered the second chapter.
Figure 9. Professor Yu Yan presided over the meeting
Figure 10. Professor Zhao Mingfang presided over the meeting
Professor Zhang Jiandong from the First Affiliated Hospital of Shandong First Medical University reported on the new practice of immunotherapy for stage III NSCLC.
Figure 11. Professor Zhang Jiandong's academic report
For stage III resectable NSCLC, AEGEAN is the first phase III clinical study of perioperative immunotherapy + neoadjuvant chemotherapy for the benefit of resectable NSCLC, and the results showed that durvalumab + chemotherapy significantly improved pathologic complete response (pCR) (difference = 13.0%) and major pathologic response (MPR) (difference = 21.0%), and significantly improved event-free survival (EFS) (HR = 0.68). A number of other phase III studies are in full swing and are changing clinical practice, showing that the full treatment model brings new treatment modalities to patients with resectable stage III NSCLC. Issues such as beneficiary population selection, efficacy evaluation, treatment mode, and other combination regimens still need to be resolved, and more phase III clinical studies are expected to be explored to guide perioperative immunotherapy models and strategies, so as to bring more benefits to patients with stage III resectable NSCLC.
For stage III uncut NSCLC, the PACIFIC study ushered in a new era of immunotherapy, with a three-fold increase in median PFS of durvalumab consolidation to a 5-year PFS rate of 33.1% and a median OS of 47.5 months, a five-year OS rate of nearly 43%. In addition, exploratory studies of expansion modes such as immune advancement and immunotherapy combination therapy continue to emerge, benefiting more patients with stage III unresectable NSCLC.
■ Ponder the treatment needs of patients with small lungs
Professor Zhang Shuang from Jilin Provincial Cancer Hospital explained the treatment strategy of SCLC.
Figure 12. Professor Zhang Shuang's academic report
The clinical benefits of extensive-phase (ES)-SCLC immunotherapy combined with chemotherapy have been fully verified, and the main ways to further enhance the benefits are chemimunization + radiotherapy and chemicomunization + anti-angiogenic inhibitors. ETER701 validated that anlotinib + PD-L1 combined chemotherapy can achieve PFS and OS breakthroughs, and the phase II study of durvalumab + anlotinib is ongoing. Concurrent chemoradiotherapy is the current standard treatment for limited-stage (LS) SCLC, and the exploration of multiple immunizations combined with concurrent chemoradiotherapy has revealed that immunotherapy can bring new benefits to patients with LS-SCLC. ADRIATIC is the first limited-time immunology study to achieve a positive Phase III result, bringing new hope to patients with SCLC.
The prognosis for patients with SCLC brain metastases is extremely poor, and OS analysis from the CASPIAN study showed that in patients with baseline brain metastases, the median OS was 11.7 months in the durvalumab + chemotherapy arm compared with 8.8 months in the chemotherapy alone group. Durvalumab + chemotherapy delays intracranial progression by up to 9 months and has been shown to delay intracranial progression in patients with ES-SCLC.
■ Discussion session
Under the chairmanship of Professor Liu Zhefeng of the Third Medical Center of the PLA General Hospital, Professor Liu Hongjie of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Professor Ma Lixia of Jilin Provincial Cancer Hospital, Professor Zou Juntao of the First Affiliated Hospital of Nanchang University, and Professor Xin Ying of Jilin Provincial Cancer Hospital discussed the hot topics of diagnosis and treatment of stage III NSCLC and SCLC.
Figure 13. Panelists
Prof. Hongjie Liu: With the success of the ADRIATIC study, the treatment pattern of "passive waiting" after concurrent chemoradiotherapy (cCRT) for patients with LS-SCLC has been broken.
Professor Ma Lixia: The heterogeneity of stage III lung cancer in mainland China is highly heterogeneous, and the diagnosis and treatment of N2 and N3 patients are controversial. For patients with stage III lung cancer who are eligible for conversion therapy, with the help of MDT, immunotherapy + chemotherapy can be tried to explore the possibility of transformation according to the patient's physical condition and precise staging.
Prof. Juntao Zou: In the past, patients with LS-SCLC usually chose etoposide chemotherapy or discontinued medication after cCRT.
Prof. Xin Ying: For patients with stage III NSCLC who are positive for driver genes, TKI therapy may be selected under the guidance of MDT and combined with the patient's own wishes.
Chapter 3 - Revolution and "New"
■ Let's talk about the whole process management of advanced lung cancer
Under the chairmanship of Professor Huang Cheng, the chairman of the conference, the conference entered the third chapter.
Figure 14. Professor Huang Cheng presided over the meeting
Professor Li Xi from Beijing Chest Hospital Affiliated to Capital Medical University shared the first-line post-drug resistance treatment strategy for EGFR mutation-positive advanced NSCLC.
Figure 15. Professor Li Xi's academic report
Common mechanisms of osimertinib resistance include C797S mutations and MET gene abnormalities, and the main treatment strategies after resistance include traditional treatment strategies and drugs using innovative mechanisms. An important regimen of traditional treatment strategies is the immunization quadruple combination regimen, such as atezolizumab + bevacizumab + paclitaxel + carboplatin, sintilimab + bevacizumab + pemetrexed + cisplatin, and the study confirmed the PFS benefit of both immunization quadruple regimens. The clinical effectiveness of rechallenging an EGFR-TKI for patients who have failed or are intolerant to first-line treatment with osimertinib is limited, but may be effective in patients with AEs leading to discontinuation.
Innovative mechanism drugs include bispecific antibodies and antibody-drug conjugates (ADCs). The TATTON and SAVANNAH studies suggest encouraging anti-tumor activity in patients with EGFR mutation-positive and MET amplification/overexpression by inhibiting both EGFR and MET signaling pathways. In the TATTON study, osimertinib + savolitinib was associated with an objective response rate (ORR) of 33% and median PFS of 5.5 months. In the SAVANNAH study, osimertinib + savolitinib was associated with an ORR of 32% and a median PFS of 5.3 months. TROP-2 ADC, HER3 ADC, EGFR× HER3 ADC showed encouraging anti-tumor activity in patients resistant to EGFR-TKI, with median PFS of 5.8 months, 5.5 months, and 5.6 months, respectively, and ORR of 43.6%, 29.8%, and 52.2%, respectively.
■ Experience the shock of innovative drugs
Professor Liu Ying from Jilin Provincial Cancer Hospital introduced the new breakthrough of new drugs in the treatment pattern of NSCLC.
Figure 16. Professor Liu Ying's academic report
ADC drugs have a long history but have only made breakthroughs in recent years, and the popular targets of lung cancer ADCs include TROP2, EGFR, HER2, HER-3, and Frα. Taking Dato-DXd, which targets TROP2, as an example, it has a comprehensive layout in the field of NSCLC, whether it is from the back line to the first line, or from single agent to combination, Dato-DXd has shown considerable therapeutic prospects in the treatment of advanced NSCLC. In the process of ADC treatment, the treatment of adverse reactions should not be ignored, and it is expected that the optimization of the process and the publication of more clinical research data will promote the progress of lung cancer treatment.
A large number of clinical research evidence suggests that bispecific antibodies (PD-1/CTLA-4, EGFR/c-Met, CD3/CLDN18.2, etc.) are another new force for breakthroughs in the diagnosis and treatment of lung cancer. With the continuous research and development of protein degraders (PROTACs, RIPTAC, LYTAC, etc.), RNA-targeted drugs, CAR-T, TCR-T and other new drugs, a diversified era of innovative drug treatment for lung cancer is coming.
■ Discussion session
Under the chairmanship of Professor Zhang Tongmei from Beijing Chest Hospital Affiliated to Capital Medical University, Professor Chen Lijuan from Zhengzhou University Cancer Hospital, Professor Cui Hongxia from Jilin Provincial Cancer Hospital, Professor Zhang Liang from Jilin Provincial Cancer Hospital, and Professor Zhang Hongmei from Beijing Chest Hospital Affiliated to Capital Medical University discussed the treatment prospects of ADC drugs.
Figure 17. Panelists
Professor Cui Hongxia: In the field of lung cancer, the ADC R&D track for targets such as TROP2, HER2, HER3, MET, and B7-H3 is very hot.
Prof. Liang Zhang: TROP2 is a very popular target in the field of lung cancer, and different TROP2 ADCs may have different clinical efficacy and advantageous populations due to different R&D platforms, linkers and payloads.
Prof. Hongmei Zhang: If there is a clear target after EGFR-TKI resistance, continue to select targeted therapy, if there is no clear target, chemotherapy + anti-vascular + immunotherapy can be considered.
Prof. Lijuan Chen: In the HER2 ADC clinical trial conducted in our hospital, the safety of lung cancer patients was good, the incidence of myelosuppression and interstitial pneumonia was low, and it was basically a grade 1 adverse reaction.
At the end of the conference, the chairmen of the conference, Professor Cheng Ying and Professor Han Baohui, pointed out in their final concluding remarks that the conference conducted in-depth academic exchanges and discussions on the cutting-edge progress in the field of lung cancer, with both width and depth, and clear and rich academic discussions, which provided a new perspective for more unresolved issues in the future. In the new era, clinicians should keep pace with the times, keep abreast of the latest cutting-edge developments, and combine the latest technologies and research results with their daily clinical work to bring more benefits to patients.
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