Genomic profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: a secondary analysis of the CLAP trial
| العنوان: | Genomic profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: a secondary analysis of the CLAP trial |
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| المؤلفون: | Chunyan Lan, Zhimin Liu, Dongqin Zhu, Fan Yang, Minjun He, Hongyu Peng, Chongjie Tong, Xiao-Long Zhang, Xin Huang, Jiani C. Yin, Junli Zhang, Yang Shao |
| المصدر: | Journal for ImmunoTherapy of Cancer, Vol 9, Iss 5 (2021) Journal for Immunotherapy of Cancer |
| بيانات النشر: | BMJ Publishing Group, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Cancer Research, Time Factors, Pyridines, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Phases of clinical research, Uterine Cervical Neoplasms, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Immunotherapy Biomarkers, Antineoplastic Combined Chemotherapy Protocols, Immunology and Allergy, Apatinib, Immune Checkpoint Inhibitors, RC254-282, Cervical cancer, biology, medicine.diagnostic_test, High-Throughput Nucleotide Sequencing, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Middle Aged, Progression-Free Survival, drug therapy, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Disease Progression, Molecular Medicine, Female, immunotherapy, Signal Transduction, Adult, medicine.medical_specialty, Combination therapy, Immunology, Antibodies, Monoclonal, Humanized, Risk Assessment, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, Biopsy, medicine, PTEN, Humans, Protein Kinase Inhibitors, PI3K/AKT/mTOR pathway, Aged, combination, Pharmacology, business.industry, Gene Expression Profiling, Immunotherapy, medicine.disease, 030104 developmental biology, chemistry, genetic markers, biology.protein, business, Transcriptome |
| الوصف: | BackgroundThe Camrelizumab Plus Apatinib in Patients with Advanced Cervical Cancer trial was a single-arm, phase II study that showed promising activity of the programmed death-1 (PD-1) inhibitor camrelizumab plus the vascular endothelial growth factor receptor-2 inhibitor apatinib in patients with advanced cervical cancer. However, the predictive biomarkers for treatment outcomes are unknown. In this study, we aimed to identify potential predictors of treatment response in PD-1 inhibitor combination therapy.MethodsGenomic profiling was performed on patients with available biopsy or surgical samples by targeted next-generation sequencing of 425 cancer-related genes in this preplanned, secondary analysis. Somatic alterations, including all non-synonymous mutations, and tumor mutational burden (TMB) were assessed for their predictive values in objective response rate, progression-free survival (PFS), and overall survival (OS).ResultsA subset of 32 patients was included in this analysis. Top altered genes included PIK3CA (43.8%), STK11 (25%), FBXW7 (15.6%), and PTEN (15.6%). The PI3K/AKT pathway was among the most frequently dysregulated pathways, and its genetic alterations were identified in 68.8% of patients. PIK3CA (PFS HR 0.33, p=0.05; OS HR 0.23, p=0.04) and PTEN (PFS HR 3.71e-09, p=0.05; OS HR 3.64e-09, p=0.08) alterations were associated with improved outcomes. PI3K/AKT pathway genetic alterations showed improved predictive power compared with either PIK3CA or PTEN alterations alone (PFS HR 0.33, p=0.03; OS HR 0.25, p=0.02), while ERBB3 mutations (PFS HR 34.9, pERBB3 mutations (PFS p=0.01, OS pConclusionsWe uncovered that genetic alterations in PIK3CA, PTEN, ERBB3, and PI3K/AKT pathway, as well as TMB, could be novel predictive biomarkers in patients with cervical cancer treated with PD-1 inhibitor combination therapy.Trial registration numberNCT03816553. |
| اللغة: | English |
| تدمد: | 2051-1426 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f04b4bdd5597fc08e7efbeb45dcf1695Test https://jitc.bmj.com/content/9/5/e002223.fullTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f04b4bdd5597fc08e7efbeb45dcf1695 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20511426 |
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