LAUSR

Objectives: The CLAP trial (NCT03816553) is a multicenter, single-arm, phase II study in patients with metastatic, recurrent, or persistent cervical cancer who were treated with PD-1 inhibitor camrelizumab plus a VEGFR2 inhibitor apatinib. In this study, we performed genomic profiling analysis to identify potential predictive biomarkers for this combination therapy. Methods: Genomic profiling was performed on 32 patients with available biopsy or surgical samples by targeted next-generation sequencing of 425 cancer-related genes. Somatic alterations and tumor mutational burden (TMB) were assessed for their predictive value on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). The Cancer Genome Atlas (TCGA) public dataset was used for validation. Results: The ORR of the current cohort was 65.6%, which was consistent with the whole CLAP population. The median PFS and OS were not reached. Frequencies of genetic alterations (PIK3CA, 43.8%; STK11, 25%; FBXW7, 15.6%; PTEN, 15.6%; TP53, 15.6%) were similar to previous reports of cervical cancer. Mutations in PI3K pathway genes were found in 68.75% (22/32) of the patients. PIK3CA mutations (57.1% vs. 18.2%, P=0.03) were significantly enriched in squamous cell carcinoma (SCC), whereas all mutations of TP53, ARID1B, DICER1, ERBB3, NF1, and TEK were detected in adenocarcinoma. Mutations in PIK3CA, PTEN, and ERBB3 were significantly associated with survival (univariate, P ≤ 0.05). PIK3CA mutations (PFS hazard ratio [HR], 0.33; P=0.05; OS HR, 0.23; P=0.04) and PTEN mutations (PFS HR, 3.71e-09; P=0.05; OS HR, 3.64e-09; P=0.08) were significantly associated with improved clinical outcome. In contrast, ERBB3 mutations (PFS HR, 34.9; P Download : Download high-res image (192KB) Download : Download full-size image Conclusions: In this study, we uncovered PIK3CA, PTEN, ERBB3, PI3K pathway genes mutations and TMB as novel predictive biomarkers in cervical cancer patients treated with PD-1 inhibitor combination therapy, which might be of great clinical relevance in patient stratification.