*For medical professionals only
The medical community will take you to see the 2024 CSCO guidelines
Finishing 丨 Sheep and sheep
From April 26th to 27th, the 2024 Chinese Society of Clinical Oncology (CSCO) guidelines meeting was held in Jinan, Quancheng. Experts and scholars from various oncology fields across the country gathered together again to clarify ideas and identify directions for the high-quality development of oncology, and jointly witnessed the update of many CSCO cancer diagnosis and treatment guidelines.
On the afternoon of the 27th, Professor Ren Shengxiang from Shanghai Pulmonary Hospital brought us the interpretation of the "CSCO Guidelines for the Diagnosis and Treatment of Primary Non-Small Cell Lung Cancer 2024 Edition" (hereinafter referred to as the Guidelines) - some of the updated points of advanced non-small cell lung cancer (NSCLC). The medical community is here to organize it for the benefit of readers.
Update summary
■驱动基因阳性晚期NSCLC
- EGFR mutations:
(1) First-line treatment of sensitive mutations: "befacitinib" is added as a level I recommendation, and "osimertinib combined with chemotherapy" is added as a level II recommendation;
(2) Second-line treatment of sensitive mutations: "befacitinib" is added as a level I recommendation
(3) 20 insertion first-line therapy: "amivantamab combined with platinum-containing doublet chemotherapy" was added as a grade III recommendation;
(4) 20 post-insertion line therapy: cancel "mobosetinib" and add "suvotinib" as a grade I recommendation
- ALK fusion positive:
(1) First-line treatment: "alectinib", "brigatinib" and "lorlatinib" are preferentially recommended, and "iluac" is added as a level I recommendation, and "iruac" is added as a level I recommendation after crizotinib resistance
- ROS1 Fusion:
新增"Repotrectinib”为III级推荐
- First-line and posterior therapy for MET exon 14 skipping protrusions:
"Terrpotinib" was upgraded to a level I recommendation, "glutatinib" and "ribritinib" were added as a level I recommendation, and "savolitinib" was added as a level II recommendation for first-line treatment
- BRAF V600突变NSCLC：
新增"Encorafenib+Binimetinib"作为III级推荐
- RET Convergence Frontline:
The type of evidence for the level I recommendation of "selpercatinib" was changed from category 3 to category 1, and the level of "pratinib" was upgraded to the level I recommendation
- HER-2 mutation posterior line:
"Detrastuzumab" was upgraded to a Level II recommendation
■无驱动基因晚期NSCLC
- First-line PS=2 part of non-squamous cell carcinoma: the addition of atezolizumab is recommended as grade II
- First-line PS=2 part of squamous cell carcinoma: the addition of atezolizumab is recommended as grade II
Treatment of stage IV driver positive NSCLC
- EGFR-sensitive mutation therapy partially updated
(1) First-line treatment of EGFR-sensitive mutant NSCLC: "Befacitinib" is added as a level I recommendation
Based on the Phase III clinical study IBIO-103, befatinib was approved by the National Medical Products Administration (NMPA) on October 12, 2023 for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R replacement mutations.
(2) First-line treatment of EGFR-sensitive mutant NSCLC: "osimertinib in combination with chemotherapy" is added as a level II recommendation
Based on FLAURA2 study, osimertinib + platinum-based chemotherapy was approved by the U.S. Food and Drug Administration (FDA) on February 16, 2024 for the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR 19 Del/L858R mutations.
(3) First-line treatment of EGFR-sensitive mutant NSCLC: "Avatomab + Lazertinib" is written into the text description
Based on the MARIPOSA study, the combination of avantuzumab and lazetinib significantly increased progression-free survival (PFS) and reduced the risk of disease progression or death by 30% compared with osimertinib (3.7 versus 16.6 months), with a median duration of response (DoR) of 25.8 versus 16.8 months in both arms.
(4) Post-line treatment of EGFR-sensitive mutant NSCLC: "Befacitinib" is added as a level I recommendation
Based on the final overall survival (OS) analysis of the IBIO-102 study, befatinib was approved by the NMPA on May 31, 2023 for the treatment of locally advanced or metastatic NSCLC with T790M mutations following prior EGFR-TKI resistance.
⑤EGFR敏感突变NSCLC后线治疗：“BL-B01D1” ( EGFR X HER3-ADC ) 写入文字描述部分
- EGFR exon 20 insertion mutation therapy section update
Figure 1. EGFR-mutant NSCLC treatment update
(1) First-line treatment of EGFR exon 20 insertion mutations: "Evantuzumab combined with chemotherapy" is added as a level III recommendation
Based on the PAPILLON study, the FDA approved evantumab in combination with carboplatin + pemetrexed on March 1, 2024 for the first-line treatment of locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations (the first first-line targeted therapy for advanced NSCLC with EGFR ex20ins mutations).
(2) Post-line treatment of EGFR exon 20 insertion mutations: "Suvotinib" is added as a level I recommendation
Based on the WU-KONG 6 study, suvotinib was approved by the NMPA on August 23, 2023 for patients with locally advanced or metastatic NSCLC who have progressed on prior chemotherapy-based chemotherapy or who have intolerant platinum-based chemotherapy and have been tested for EGFR exon 20 insertion mutations.
- ALK fusion positive treatment partial update
(1) First-line treatment of ALK fusion NSCLC: "Iruak" is added as a level I recommendation
Based on the INSPIRE study, Iruak was approved by the NMPA on January 16, 2024 for the first-line treatment of ALK-positive locally advanced or metastatic NSCLC.
(2) First-line treatment of ALK fusion NSCLC: "Yibong Acker" is written into the text description
Figure 2.Key clinical results of a multicenter, randomized controlled phase III clinical study (NCT04009317) of ebongacon vs. crizotinib in the first-line treatment of ALK-positive advanced NSCLC
(3) Post-line treatment of ALK fusion NSCLC: "Iluac" is recommended as grade I after crizotinib resistance
Based on the INTELLECT study, Iluac was approved by the NMPA on June 28, 2023 for ALK-positive locally advanced or metastatic NSCLC that has progressed after prior treatment with crizotinib or is intolerant to crizotinib.
- ROS1 fusion-positive treatment partially updated
①ROS1融合NSCLC一线治疗：新增“Repotrectinib”为III级推荐
②ROS1融合NSCLC后线治疗: 新增“Repotrectinib”为III级推荐
Based on the TRIDENT-1 study, repotrectinib was granted Priority Review approval by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) on May 10, 2023, and was approved by the FDA on November 15, 2023 for the treatment of adult patients with ROS1-positive locally advanced or metastatic NSCLC. The two updates are the results of the TRIDENT-1 study Cohort 1 (Repotrectinib for ROS1-TKI-naïve advanced or metastatic NSCLC) versus Cohort 4 (Repotrectinib for ROS1-TKI-experienced locally advanced or metastatic NSCLC).
(3) Post-line treatment of ROS1 fusion NSCLC: anekitinib was included in the text description
Figure 3.Efficacy and safety of a phase III study of anekitinib in the posterior treatment of ROS1-positive NSCLC
- BRAF V600 /MET 14 外显子/RET 融合/HER-2突变部分更新
图4. BRAF V600/NTRK/MET 14外显子/RET/KRAS G12C/HER-2 突变NSCLC的一线治疗
①BRAF V600突变NSCLC一线治疗: 新增“Encorafenib+ Binimetinib”为III级推荐
Based on the results of the PAROS study, encorafenib in combination with binimetinib was approved by the FDA on October 11, 2023 for the treatment of patients with metastatic NSCLC with BRAF V600E mutations.
(2) First-line treatment of MET exon 14 skipping mutation NSCLC: "texon-14" was up-regulated as a level I recommendation
Based on the VISION study, tepotinib received accelerated approval from the FDA on February 3, 2021 and NMPA approval for the treatment of advanced or metastatic NSCLC with MET14 exon skipping mutations on December 5, 2023.
(3) First-line treatment of MET exon 14 skipping mutation NSCLC: "glutatinib" is added as a grade I recommendation
Based on the GLORY study, glutatinib received conditional approval from the NMPA on March 8, 2023 for the treatment of locally advanced or metastatic NSCLC with MET exon 14 skipping mutations.
(4) First-line treatment of MET exon 14 skipping mutation NSCLC: "briitinib" is added as a level I recommendation
Based on the KUNPENG study, britinib received conditional approval from the NMPA on November 16, 2023 for the treatment of locally advanced or metastatic NSCLC with MET14 exon skipping mutations.
(5) First-line treatment of MET exon 14 skipping mutation NSCLC: savolitinib is recommended as grade III
Based on a Phase IIIb study of savolitinib in MET exon 14 skipping mutant NSCLC, savolitinib had an objective response rate (ORR) of 61.2% and PFS of 13.7 months in 87 treatment-naïve patients. At present, the marketing application of savolitinib for the treatment of locally advanced or metastatic NSCLC with MET14 exon skipping alterations has been accepted by the NMPA.
(6) First-line treatment of RET fusion NSCLC: The type of evidence for the level I recommendation of "selpercatinib" was changed from category 3 to category 1
Based on the LIBRETTO-001 study, selpercatinib received conditional approval from the NMPA on September 30, 2022 for the treatment of patients with RET fusion-positive NSCLC, and the LIBRETTO-431 study met the primary endpoint, further confirming the efficacy of selpercatinib as a first-line treatment.
(7) First-line treatment of RET fusion NSCLC: "Platinib" was up-adjusted to the level I recommendation
Platinib was routinely approved by the FDA on August 9, 2023, and the Chinese population data from the ARROW study suggest that pratinib has good anti-tumor activity in first-line RET-positive patients, and pratinib was approved by the NMPA on June 26, 2023 for the first-line treatment of adult patients with RET fusion-positive NSCLC.
图5. BRAF V600/NTRK/MET 14外显子/RET/KRAS G12C/HER-2 突变NSCLC的后线治疗
(8) Post-line treatment of MET exon 14 skipping mutation NSCLC: "textratinib" was up-regulated as a grade I recommendation
In the VISION study, tepotinib also had anti-tumor effects in the second-line treatment of patients with MET exon 14 skipping mutation NSCLC. As a result, tepotinib received accelerated FDA approval on February 3, 2021 and NMPA approval on December 5, 2023 for the treatment of advanced or metastatic NSCLC with MET14 explicit skipping mutations.
(9) Post-line treatment of MET14 exon skipping mutation NSCLC: "britinib" is added as a level I recommendation
Based on the KUNPENG study, britinib received conditional approval from the NMPA on November 16, 2023 for the treatment of locally advanced or metastatic NSCLC with MET14 exon skipping mutations.
(10) Post-line treatment of HER-2 mutant NSCLC: up-regulated "trastuzumab" as a level II recommendation
In the DESTINY-Lung02 study, the ORR in the Asian population was 50.8% and 73.3%, respectively, consistent with the population-wide benefit trend, and trastuzumab received accelerated FDA approval for the treatment of unresectable or metastatic HER2-mutant NSCLC previously treated with systemic therapy on August 11, 2022, and was granted Breakthrough Therapy Designation by the CDE on January 3, 2024.
Figure 6. KRAS inhibitors such as Garsorasib (D-1553), IBI351, and JDQ443 were included in the text description
IVSCLC
- First-line treatment PS=0~1 part: Notes part updated
(1) Note: Immunotherapy has become the standard first-line treatment for driver-negative advanced non-squamous NSCLC, so this guideline moves the recommended immunotherapy regimen forward.
(2) Note: The CSCO guidelines recommend 7 different immunotherapy regimens combined with chemotherapy, and the PFS and OS results of each study are summarized for clinicians to use as a reference when choosing treatment regimens.
Figure 7. Summary of survival data in phase III study of first-line immunotherapy in phase IV non-squamous NSCLC without driver genes
- First-line treatment PS=2 part: "atezolizumab" is added as a level I recommendation
In the Asian population analysis of the Phase III study of IPSOS comparing atezolizumab with single-agent chemotherapy for first-line treatment in patients with NSCLC who are not candidates for platinum-based chemotherapy, PS=2 accounted for 82.9%, consistent with OS and safety in the global ITT population, and atezolizumab provided a survival benefit for patients with PS=2.
- Second-line and post-line treatments: The second-line treatment of Dato-DXd is written in the text description
图8. TROPION-lung01: Dato-DXd vs 多西他赛治疗经治NSCLC的III期研究结果
Treatment of stage IV driver-free, squamous cell carcinoma
- First-line treatment PS=0~1 part: Notes part updated
Figure 9. Summary of survival data from the phase III study of first-line immunotherapy in squamous NSCLC without driver genes
Annotation update: The CSCO guidelines recommend 7 different immunotherapy regimens combined with chemotherapy, and the PFS and OS results of each study are summarized for clinicians to use as a reference when choosing a treatment regimen.
- First-line treatment PS = 2 part: "atezolizumab" was up-regulated to the level II recommendation
The PS=2 part of the first-line treatment of NSCLC with no driver gene and non-squamous cell carcinoma in stage IV was updated.
Exciting information is waiting for you
Editor in charge: Sheep
*The medical community strives to be professional and reliable in its published content, but does not promise the accuracy of the content.