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iNature
Lung cancer is the leading cause of cancer death globally and in China, with the highest incidence of all cancers worldwide, with about one-third of new cases and cancer deaths in China alone
.
Non–small-cell lung cancer (NSCLC) accounts for about 85% of all lung cancers and is the leading cause of
cancer-related death.
For patients with advanced NSCLC without driver mutations, conventional platinum-based chemotherapy has been the standard first-line treatment, but clinical efficacy is not ideal
.
On October 7, 2022, Wang Jie's team from the Cancer Hospital of the Chinese Academy of Medical Sciences published an online publication in the Journal of Clinical Oncology entitled " Toripalimab Plus Chemotherapy for Patients With Treatment-Naive Advanced Non–Small-Cell Lung Cancer: A Multicenter Randomized Phase III Trial (CHOICE-01) The randomized, double-blind, placebo-controlled phase III study (CHOICE-01) compared the efficacy and safety
of Toripalimab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for patients with advanced NSCLC without EGFR/ALK-driven mutations.
The study demonstrated that the addition of Toripalimab to chemotherapy in untreated patients with advanced NSCLC was superior to chemotherapy with a manageable safety profile
over chemotherapy alone.
These results support Toripalimab monoclonal antibody combined with chemotherapy as first-line treatment
for patients with advanced NSCLC without EGFR/ALK mutations.
of advanced NSCLC because of their superior efficacy over traditional chemotherapy.
Large-scale clinical trials support anti-PD-1/PD-L1 combination chemotherapy as standard first-line therapy
for advanced NSCLC without driver mutations.
However, identifying predictive biomarkers for beneficial patient populations needs to be further explored
.
Therefore, large-scale clinical trials of first-line chemotherapy immunotherapy for NSCLC, comprehensive endpoint analysis and biomarker exploration are still necessary
.
Through crystal structure analysis, Torpalimab is a humanized IgG4K monoclonal antibody that is specific to human PD-1
.
This monoclonal antibody has a differential domain
with nivolumab and pembrolizumab on PD-1.
In a preclinical study, Torpalimab promoted antigen-specific interferon-γ production more than nivolumab CHOICE-01 is a multicenter, randomized, double-blind, placebo-controlled phase III study conducted
in 59 medical centers in China.
Eligible patients must be untreated, locally advanced (stage IIIB or IIIC), or metastatic NSCLC, or have completed neoadjuvant/adjuvant therapy
at least 6 months prior to enrollment.
Patients with non-squamous NSCLC with EGFR or ALK-driven mutations were excluded
.
In this study, researchers randomized 465 eligible patients in a 2:1 ratio to receive Toripalimab 240 mg (N = 309) or placebo (N = 156) every 3 weeks, in combination with chemotherapy for 4-6 cycles, followed by torlipril monolithic or placebo every 3 weeks, plus standard care
.
Stratifying factors included programmed death ligand-1 (PD-L1) expression status, histology, and smoking status
.
The primary endpoint is PFS (refers to the time from the beginning to the occurrence of arbitrary tumor progression or death) according to the RECIST v1.
1 (Response Evaluation Criteria in Solid Tumors).
Secondary endpoints included overall survival and safety
.
Fig.
1.
Assessment of PFS curves for two therapies in untreated populations (Figure from Journal of Clinical Oncology) In the final PFS analysis, PFS in the Torpalimab monoclonal antibody group was significantly longer than in the placebo group (median PFS 8.
4 v 5.
6 months, hazard ratio = 0.
49; 95% CI, 0.
39 ~ 0.
61; two-sided P <.
0001).
In the interim OS analysis, OS was significantly longer in the torpalimab group than in the placebo group (median OS did not reach 17.
1 months, hazard ratio = 0.
69; 95% CI, 0.
53 ~ 0.
92; two-sided P = .
0099)
。 The incidence of grade 3 adverse events was similar
between the two groups≥ Treatment effects were similar
regardless of PD-L1 status.
Figure 2.
Evaluation of the OS curves of the two therapies in the untreated population (Figure from Journal of Clinical Oncology).
Further genomic analysis of whole exome sequencing of 394 tumor samples showed that PFS (median PFS 13.
1 v 5.
5 months, interaction P = .
026) in the combined group was significantly better than that in patients with high TMB (≥10 mutations/Mbp) or FA-PI3K-Akt, IL-7 signaling pathway or SWI/SNF complex mutations
.
Notably, patients with mutations in the FA-PI3K-Akt pathway also gained significantly better overall survival benefits
from combination therapy.
Taken together, the results of this study suggest that in patients with advanced NSCLC, Torpalimab combination chemotherapy significantly improves progression-free survival and overall survival compared with chemotherapy alone, while having a manageable safety profile
.
Therefore, this study supports the combination of torpalimab monoclonal antibody and chemotherapy as a first-line treatment option for patients with advanced NSCLC without EGFR/ALK driver mutations, and provides a new perspective
for patient selection based on tumor genetic alterations.
Original link: https://ascopubs.
org/doi/full/10.
1200/JCO.
22.
00727
—END—
The content is 【iNature】
