A study of gene variation in All- RAS wild-type metastatic colorectal cancer and its correlation with cetuximab

Journal of Gastrointestinal Oncology

article

Huimin Tao¹  Meng Shen¹  Xiaochang Zhang¹  Minghui Wang¹  Yan Wu¹  Hui Sun¹  Chen Ling¹  Ying Yang¹  Kai Chen¹  Dapeng Li¹ 

[1] Department of Oncology, The First Affiliated Hospital of Soochow University

关键词: Metastatic colorectal cancer (mCRC);    second-generation sequencing;    cetuximab;    gene alteration;    prognosis;   

DOI  :  10.21037/jgo-22-1237

学科分类：肿瘤学

来源: Pioneer Bioscience Publishing Company

【 摘 要 】

Background: This study sought to explore the biological significance of genetic variation in RAS wild-type metastatic colorectal cancer (mCRC) in the real world, the difference in the efficacy of cetuximab in the treatment of mCRC with different genetic variants and identify clinical features and new predictors of efficacy. Methods: A retrospective analysis of the data of 60 patients with stage IV mCRC who received cetuximab at The First and Second Affiliated Hospital of Soochow University from 2016 to 2020 was conducted. The patients were divided into the following 3 groups according to the genetic test results: (I) group A (the all-RAS wild-type group); (II) group B (the all-RAS wild-type group with the tumor suppressor gene mutation); and (III) group C (the all-RAS wild-type group with the oncogenic driver gene mutation). A subgroup analysis was conducted to examine left CRC and local intervention, and the progression-free survival (PFS) and overall survival (OS) of the patients were observed. Results: The all-RAS wild-type mCRC patients were divided into group A (n=10), group B (including the TP53, APC, PTEN, BRCA2, and SMAD4 variants) (n=42), and group C (including the ERBB2, BRAF, PIK3CA, and RET variants) (n=8). The median PFS of groups A, B, and C were 15.0, 12.0, and 3.0 months, respectively (P=0.007). Fitting sex as a stratified variable to the Cox survival analysis model showed that only the PFS of groups B and C differed significantly (P=0.011). In the left-sided mCRC patients, the median PFS of groups A, B, C were 3.0, 13.0, and 3.0 months, respectively (P=0.009). Among the patients in group B, the median PFS of the metastatic local intervention subgroup was 14.0 months, and the non-local intervention subgroup was 12.0 months (P=0.55). Only the type of combined gene mutation was an independent factor affecting PFS. Conclusions: The PFS and OS of mCRC patients with all-RAS wild-type and no combined mutations treated with cetuximab were not better than those of patients with combined mutations. Compared to mCRC patients with all-RAS wild-type and oncogenic driver gene mutations, cetuximab significantly prolonged the PFS of all-RAS wild-type patients with the tumor suppressor gene mutations.

【 授权许可】

Unknown