*For medical professionals only
This article summarizes the updated content of targeted therapy in the CSCO non-small cell lung cancer guidelines!
On April 26-27, 2024, the CSCO Guidelines Conference jointly sponsored by the Chinese Society of Clinical Oncology (CSCO) and Beijing Heathosco Clinical Oncology Research Foundation was held in Jinan, and the 2024 edition of the CSCO clinical diagnosis and treatment guidelines was officially released at the conference.
In the 2024 edition of the CSCO NSCLC diagnosis and treatment guidelines, targeted therapy is undoubtedly a "big star": whether it is for patients who are operable in the early and middle stages or those who are positive for advanced driver genes, the CSCO guidelines are effective in molecular typing, There are many updates in target detection and treatment options, such as recommending that ALK fusion should be tested for patients who are operable in the early and middle stages, and recommending adjuvant alectinib therapy for ALK fusion-positive patients for the first time after surgery, which also means that alectinib is the first ALK-TKI to cover patients with early, middle and advanced NSCLC. Professor Zhou Caicun from the East Hospital Affiliated to Tongji University was invited to share the updated content of the guidelines.
Expert Profile
Zhou Caicun
Chief physician, professor and doctoral supervisor
- Department of Oncology, Shanghai East Hospital
- Director of the Institute of Oncology, Tongji University School of Medicine
- President-elect of the International Association for the Study of Lung Cancer (IASLC).
- Chairman of the Thoracic Oncology Branch of the China Medical Promotion Association
- Chairman of the Non-Small Cell Lung Cancer Committee of the Chinese Society of Clinical Oncology
- Chairman of the Clinical Research Committee of Cancer Drugs of the Chinese Anti-Cancer Association
- Chairman of the Lung Cancer Molecular Targeting and Immunotherapy Committee of Shanghai Anti-Cancer Association
- Member of the Standing Committee of the Oncology Branch of the Chinese Medical Doctor Association
- Vice Chairman of Shanghai Anti-Cancer Association
- Vice President of Oncology Branch of Shanghai Medical Doctor Association
- Vice Chairman of Oncology Branch of Shanghai Medical Association
Summary of the 2024 CSCO Guidelines for Targeted Therapy Updates:
There are flashes in the early, mid and late updates
Updates on some targeted therapies for the diagnosis and treatment of early- and medium-term NSCLC:
■ Molecular typing update
Grade II recommended addition: ALK fusion detection for postoperative stage II/III NSCLC to guide adjuvant targeted therapy;
Grade II recommended addition: immunohistochemical MET protein overexpression detection in inoperable stage III and IV NSCLC tumor tissues.
Figure 1.Molecular typing update for early-to-mid-stage NSCLC
■ Surgical stage IIA and IIB NSCLC treatment updates
Adjuvant targeted therapy
Grade II recommendation added: Adjuvant alectinib postoperatively for patients with radical surgery and postoperative detection of ALK fusion.
■ 可手术IIIA或IIIB期NSCLC的治疗更新
Adjuvant targeted therapy
Grade II recommendation added: Adjuvant alectinib postoperatively for patients with radical surgery and postoperative detection of ALK fusion.
Figure 2. CSCO guidelines recommend adjuvant alectinib after surgery based on the ALINA study
Treatment of stage IV driver-positive non-small cell lung cancer
■ EGFR mutations
Grade I recommendations for first-line treatment of sensitive mutations: befacitinib, and grade II recommendations: osimertinib plus chemotherapy;
Level I recommendations for second-line treatment of sensitive mutations have been added: befacitinib;
20 Exome insertion first-line treatment for grade III recommended addition: amivantamab in combination with platinum-doublet chemotherapy;
20 After exon insertion, it is recommended to cancel mobosetinib and add suvotinib.
■ ALK fusion positive
Among the first-line treatment level I recommendations, alectinib, brigatinib, lorlatinib are preferred;
Grade I recommendations for post-line therapy have been added: Iruac (limited to first-line crizotinib resistance).
■ ROS1 fusion positive
一线治疗和二线治疗III级推荐新增：Repotrectinib。
■ WITH 14外显子跳突
The first-line treatment level II recommendation was added: glutatinib and tepotinib were upgraded to level I recommendation, braitinib was added as level I recommendation, and savolitinib was added as level II recommendation.
The first-level recommendation for post-line treatment was added: glutetinib and braitinib, and the recommendation of tepotinib was upgraded to level I.
■ BRAF V600突变
一线治疗III级推荐新增:Encorafenib+Binimetinib。
■ RET fusion
The first-line treatment of selpercatinib was changed from a category 3 to a category 1, and the level of platinib was upgraded to a level I recommendation.
■ HER-2突变
In the later line of therapy, detrastuzumab is up-regulated as a grade II recommendation.
Figure 3.Summary of the updated treatment of early- and mid-stage NSCLC
ALINA research successfully "reached the top",
Adjuvant alectinib is among the guideline recommendations
It can be seen from the update of the 2024 CSCO NSCLC diagnosis and treatment guidelines that targeted therapy for driver gene variants not only continues to develop rapidly in advanced NSCLC, but also begins to gradually change the perioperative treatment of early-to-mid-stage NSCLC, bringing more accurate and efficient neoadjuvant/ Adjuvant therapy is the first perioperative precision treatment regimen for ALK fusion-positive patients, and the recommendation is based on the interim analysis of ALINA, a pivotal phase III clinical study that was recently published in the New England Journal of Medicine [1].
The ALINA study is a global, Phase III, open-label, randomized controlled clinical study to analyze the efficacy and safety of adjuvant alectinib compared with conventional adjuvant platinum-based chemotherapy in patients with ALKFUSION-positive stage IB-IIIA (UICC/AJCC 7th edition) NSCLC after radical resection.
The results of the interim analysis of the ALINA study showed that in patients with stage II-IIIA, the 2-year DFS rate was 93.8% and 88.3% in the alectinib group, compared with 63.0% and 53.3% in the chemotherapy group, although the median DFS of patients in the alectinib group was not reached, compared with the chemotherapy group, alectinib treatment reduced the risk of disease recurrence, metastasis or death by 76% compared with the chemotherapy group (HR=0.24, 95% CI: 0.13-0.45, P＜0.001）。
The 2-year DFS rate (93.6% vs. 63.7%) and 3-year DFS rate (88.7% vs. 54.0%) in the alectinib group were also significantly higher than those in the chemotherapy group, and alectinib treatment also reduced the risk of disease recurrence, metastasis or death by 76% (HR=0.24, 95% CI: 0.13-0.43, P<0.001).
Figure 4.DFS data for alectinib in the stage II-IIIA and overall intention-to-treat populations
At the same time, the safety profile of the 2-year adjuvant alectinib therapy was also generally good, no new safety signals were found in the study, and the safety profile of alectinib treatment was also consistent with the known safety profile, and the most common adverse events in patients (incidence ≥20%) included increased creatinine, constipation, nausea, loss of appetite, etc., but the incidence of grade 3 treatment-related adverse events (TRAEs) was lower ≥in the alectinib group (18.0% vs. 27.5%), and the proportion of patients discontinuing the drug due to adverse events was lower (5.5% vs. 27.5%). 12.5%）。
Based on the above favorable efficacy and safety data from the ALINA study, the U.S. FDA has officially approved the new indication of adjuvant alectinib on April 18, 2023, and the latest version of the National Comprehensive Cancer Network (NCCN) NSCLC Clinical Practice Guidelines (2024.V5) has also recommended adjuvant alectinib for ALK fusion-positive stage II-IIIA patients and stage IIIB patients with T3N2 in the latest version of the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines (2024.V5).
The adjuvant alectinib therapy has successfully entered the CSCO It is believed that after the indication is officially approved, adjuvant alectinib will soon be widely used in clinical practice, and under the authoritative guidance of the CSCO guidelines, it will bring significant clinical benefits to the majority of ALK fusion-positive operable patients, further reduce the risk of postoperative disease recurrence or death, and hope to significantly improve the long-term prognosis of such patients.
Bibliography:
[1] Wu Y L, Dziadziuszko R, Ahn J S, et al. Alectinib in Resected ALK-Positive Non–Small-Cell Lung Cancer[J]. New England Journal of Medicine, 2024, 390(14): 1265-1276.
[2] Ahn J S, Wu Y L, Dziadziuszko R, et al. LBA1 Efficacy and safety of adjuvant alectinib vs platinum-based chemotherapy (CT) in patients (pts) from Asia with resected, early-stage ALK+ non-small cell lung cancer (NSCLC): A sub analysis of ALINA[J]. Annals of Oncology, 2023, 34(Supplement 4): S1646-S1647.
Exciting information is waiting for you
* This article is only for the purpose of providing scientific information to medical professionals and does not represent the views of this platform