2024年CSCO晚期非小细胞肺癌指南更新

Updates to the 2024 CSCO advanced non-small cell lungcancer guidelines Jiale Wang1,2, Tianyu Qiu1,2, Shengxiang Ren1,21School of Medicine, Tongji University, Shanghai 200331, China;2Department of Medical Oncology, Shanghai PulmonaryHospital, School of Medicine, Tongji University, Shanghai 200433, China Advanced NSCLC with driver genemutations In the past year, several advancements have been achievedin the treatment of advanced non-small cell lung cancer(NSCLC), particularly in the areas of immunotherapy and tar-geted therapy. These achievements have provided additionaloptions for improving patient outcomes. The 2024 ChineseSociety of Clinical Oncology Guidelines for NSCLC (CSCONSCLC), a key reference for clinical oncologists in China, haveincorporated current global research and adapted recommen-dations for applicability in real-world scenarios in China. Thisupdate covers not only patient selection, efficacy, and safety,but also considers economics, and accessibility, with an aim toprovide more precise and comprehensive treatment guidancefor Chinese oncologists. Common driver gene mutations Numerous clinical studies and targeted therapies concern-ingEGFRmutations, the most prevalent driver mutationsin NSCLC in China, have emerged in recent years. Third-generationEGFRinhibitors such as osimertinib, furmoner-tinib, and almonertinib have been successfully introduced.On the basis of the results from the IBIO-103 and IBIO-102studies,the fourth third-generation EGFR-targeted ther-apy befotertinib has become available. Compared with ico-tinib,befotertinib significantly prolongs progression-freesurvival (PFS) as a first-line treatment [22.1 monthsvs.13.8months, Hazard Ratio (HR) = 0.49,P< 0.0001]1. For patientswith T790M mutations, befotertinib has also demonstrateda promising objective response rate (ORR) of 66.2%, with amedian overall survival (OS) of 31.5 months2. On the basisof these data, the National Medical Products Administration(NMPA) approved befotertinib for both first- and second-linetreatment of patients withEGFRmutations, and has includedthis grade I recommendation in the 2024 CSCO, thus furthersolidifying the role of third-generationEGFRinhibitors in thetreatment of advanced NSCLC. The targeted therapy guidelines have been revised forEGFR,ALK,RET, andMETmutations, to provide practical,future-oriented recommendations for oncogenic driver muta-tions. For patients with NSCLC without oncogenic drivermutations and with a performance status of 2, atezolizumabhas been included as a grade II front-line recommendation,thereby highlighting the importance of immunotherapy in thiscohort. Furthermore, novel treatment approaches such as anti-body-drug conjugates (ADCs) are being actively investigatedand have shown promising potential. This article describes keyupdates offering enhanced guidance for clinical practice andcontributing to the advancement of lung cancer care quality. To address the limited efficacy of monotherapy, researchershave explored combinations of targeted therapies and othertreatments. In the phase III FLAURA2 trial, osimertinib com-bined with chemotherapy significantly prolonged PFS (25.5monthsvs.16.7 months, HR = 0.62,P< 0.001) and showed atrend toward OS benefit, with no significant increase in adverseeffects3. FLAURA2 established osimertinib-chemotherapy asa new first-line treatment forEGFRNSCLC; this treatmenthas been approved by both the NMPA and Food and Drug achieve significantly longer PFS than crizotinib. Additionally,after the INSPIRE study, the NMPA approved iruplinalkibas a first-line treatment forALK-fusion advanced NSCLCon January 16, 2024, on the basis of clinical data showing amedian PFS of 27.7 months, compared with 14.6 months withcrizotinib (HR = 0.34,P< 0.0001)7. Furthermore, iruplinalkibdemonstrated high efficacy as a second-line treatment, with anORR of 69.9% in the INTELLECT study, thus further confirm-ing its clinical value8. Another promising medicine targetingc-Met/ALK/ROS1 is envonalkib. Compared with crizotinib,envonalkib significantly extends the median PFS in patientswithALKfusion (24.9 monthsvs.11.6 months, HR = 0.47,P< 0.0001) and was approved by NMPA as a first-line treat-ment in June 20249. With the approval of these therapies, theoptions forALK-targeted medicine have become increasinglyrobust. Currently, 8 drugs have been approved in China forALK-fusion NSCLC, including 6 international drugs and 2domestic drugs. Administration (FDA). Additionally, in the MARIPOSA studya combination of lazertinib and amivantamab (EGFR-METbispecific antibody), compared with osimertinib, significantlyextended the PFS (23.7 monthsvs.16.6 months, HR = 0.70,P< 0.001)4. However, because neither drug has been introducedin China, this combination is included only in the descriptivesection of the updated guidelines. In the MARIPOSA-2 trial,PFS was significantly longer for amivantamab–chemotherapyand amivantamab–lazertinib–chemotherapyvs.chemother-apy (6.3 and 8.3vs.4.2 months,