This article is original from Translational Medicine Network. Please indicate the source when reprinting
Author: Mia
Introduction: In recent years, immunotherapy has developed rapidly, bringing new hope to patients with advanced lung cancer. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. NSCLC is one of the leading causes of cancer-related deaths and is also the most common cancer in all cancers worldwide. There are large-scale clinical trials that support anti-PD-1/PD-L1 combined with chemotherapy as standard first-line treatment for advanced NSCLC without driver mutations. However, further exploration of predictive biomarkers that can identify beneficiary patient populations is needed.
On October 7, 2022, Professor Wang Jie's team of Hankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankankan This study investigated the efficacy and safety of Torpalimab combined with chemotherapy as the first-line treatment of advanced non-small cell lung cancer (NSCLC).
https://ascopubs.org/doi/10.1200/JCO.22.00727
Research background
01
Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. NSCLC is one of the leading causes of cancer-related deaths and is also the most common cancer in all cancers worldwide. China accounts for about one-third of the world's new cases and cancer deaths. In patients with advanced NSCLC without driver mutations, traditional platinum chemotherapy has been the standard first-line treatment despite unsatisfactory clinical benefits.
, an immune checkpoint inhibitor represented by programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) antibodies, significantly changed the current treatment status of advanced NSCLC because its efficacy is better than traditional chemotherapy. There are large-scale clinical trials that support anti-PD-1/PD-L1 combined with chemotherapy as standard first-line treatment for advanced NSCLC without driver mutations. However, also needs to further explore predictive biomarkers that can identify beneficiary patient populations. Therefore, it is necessary to conduct a comprehensive and comprehensive endpoint analysis and biomarker exploration of rigorously designed large-scale clinical trials for NSCLC first-line chemotherapy immunotherapy.
Torpalimab is a humanized IgG4K monoclonal antibody, which is specific to human PD-1. Through crystal structural analysis, it was found that it had different domains on PD-1 from nivolumab and pembrolizumab. In a preclinical study, torpalimab promotes antigen-specific interferon-γ production more than nivolumab. Early clinical trials of Toripalimab also showed promising antitumor activity in advanced NSCLC.
study overview
02
In the CHOICE-01 study, researchers compared the efficacy and safety of toripalimab plus chemotherapy with placebo plus chemotherapy as the first-line treatment of advanced NSCLC patients without EGFR/ALK driver mutations.
CHOICE-01 is a multi-center, randomized, double-blind , placebo-controlled phase III study conducted in 59 medical centers in China. Eligible patients must be non-squamous NSCLC patients who have completed neoadjuvant/adjuvant therapy at least 6 months before enrollment and excluded EGFR or ALK-driven mutations.
patients were randomly assigned at a ratio of 2:1 and received toripalimab or placebo plus chemotherapy respectively. Patients were given toripalimab or placebo 240 mg every 3 weeks and maintained a basic care regimen. Tumor assessment was performed at baseline, every 6 weeks during the first 12 months and every 9 weeks thereafter. The results of
progression-free survival (PFS) and overall survival (OS) analysis showed that compared with , the addition of toripalimab in standard first-line chemotherapy, showed significant statistically significant and clinically significant improvements in regardless of PD-L1 expression.
researchers also used whole-exome sequencing to perform genome analysis of tumor biopsy and paired PBMCs. Further analysis revealed mutations in genes that significantly interacted with therapeutic effects, including RB1, KEAP1 and SMARCA4.Patients carrying SMARCA4 mutations, especially in the nonsquamous subgroup (n = 33), PFS in the toripalimab group was significantly better than those in the placebo group. In contrast, patients with RB1 mutation (n = 21) in the squamous subgroup had worse PFS than the placebo group, suggesting that they may not benefit from combination therapy.
study summary
03
In summary, the study revealed that the addition of toripalimab to chemotherapy in patients with advanced NSCLC who were not treated is better than chemotherapy alone, and has controllable safety. These results support the use of toripalimab in combination with chemotherapy as the first-line treatment for patients with advanced NSCLC without EGFR/ALK mutations.
Reference materials:
https://ascopubs.org/doi/10.1200/JCO.22.00727
Note: This article aims to introduce the progress of medical research and cannot be used as a reference for treatment plans. If you need health guidance, please go to a regular hospital for treatment.
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