Genomic profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: a secondary analysis of the CLAP trial

• DOI: 10.1136/jitc-2020-002223
• Publication Date: 2021-05-19T17:36:44Z
• Authors: Xin Huang; Minjun He; Hongyu Peng; Chongjie Tong; Zhimin Liu; Xiaolong Zhang; Yang Shao; Dongqin Zhu; Junli Zhang; Jiani C Yin; Fan Yang; Chunyan Lan
• Keywords: STK11; Progression-free survival

Background The 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 vascular endothelial growth factor receptor-2 apatinib patients advanced cervical cancer. However, predictive biomarkers for treatment outcomes are unknown. In this study, we aimed to identify potential predictors response PD-1 combination therapy. Methods Genomic profiling performed on available biopsy or surgical samples by targeted next-generation sequencing 425 cancer-related genes preplanned, secondary analysis. Somatic alterations, including all non-synonymous mutations, and tumor mutational burden (TMB) were assessed their values objective rate, progression-free survival (PFS), overall (OS). Results A subset 32 included Top altered PIK3CA (43.8%), STK11 (25%), FBXW7 (15.6%), PTEN (15.6%). PI3K/AKT pathway among most frequently dysregulated pathways, its genetic alterations identified 68.8% patients. (PFS HR 0.33, p=0.05; OS 0.23, p=0.04) 3.71 e-09 , 3.64 p=0.08) associated improved outcomes. power compared either alone p=0.03; 0.25, p=0.02), while ERBB3 mutations 34.9, p<0.001; 19.8, p<0.001) correlated poor survival. TMB-high (≥5 mut/Mb) prolonged PFS (HR 0.26, p<0.01) 0.31, p=0.05). Multivariate analysis p=0.01, p<0.001), PD-L1 positive p=0.05), high TMB p=0.05) remained significantly Conclusions We uncovered pathway, as well TMB, could be novel cancer treated Trial registration number NCT03816553 .