Oxaliplatin-Based Chemotherapy Is More Beneficial in KRAS Mutant than in KRAS Wild-Type Metastatic Colorectal Cancer Patients

Abstract

To identify better regimens in currently available chemotherapy would be beneficial to KRAS mutant metastatic colorectal cancer (mCRC) patients because they have fewer treatment options than KRAS wild-type mCRC patients. Clinicopathologic features and overall survival (OS) of KRAS mutant and wild-type mCRC patients who had used oxaliplatin-based, irinotecan-based, bevacizumab-based, as well as cetuximab-based regimens were compared to those who had never-used oxaliplatin-based, irinotecan-based, bevacizumab-based, as well as cetuximab-based regimens respectively. Between 2007 and 2012, a total of 394 mCRC patients, in whom 169 KRAS mutant and 225 KRAS wild-type, were enrolled. In KRAS mutant patients who had used oxaliplatin-based regimens (N = 131), the OS was significantly longer than that in KRAS mutant patients who had never-used oxaliplatin-based regimens (N = 38). The OS was 28.8 months [95% confidence interval (CI): 23.2–34.4] in KRAS mutant patients who had used oxaliplatin-based regimens versus 17.8 months [95% CI: 6.5–29.1] in KRAS mutant patients who had never-used oxaliplatin-based regimens (P = 0.026). Notably, OS in KRAS wild-type mCRC patients who had used oxaliplatin-based regimens (N = 185) was not significantly longer than that in KRAS wild-type mCRC patients who had never-used oxaliplatin-based regimens (N = 40) (P = 0.25). Furthermore, the OS in KRAS mutant patients who had used either irinotecan-based, bevacizumab-based or cetuximab-based regimens was not significantly different than that in KRAS mutant patients who had never-used either irinotecan-based, bevacizumab-based or cetuximab-based regimens respectively. In multivariate analyses, patients who had used oxaliplatin-based regimens remains an independent prognostic factor for longer OS in KRAS mutant mCRC patients. In conclusion, oxaliplatin-based regimens are more beneficial in KRAS mutant than in KRAS wild-type mCRC patients.

KRAS and BRAF Mutations as Prognostic and Predictive Biomarkers for Standard Chemotherapy Response in Metastatic Colorectal Cancer: A Single Institutional Study

“…Lin et al suggested KRAS mutation as a predictor of oxaliplatin sensitivity in vitro by downregulation of ERCC1 [53]. Indeed, a benefit of oxaliplatin-based chemotherapy for KRAS mutated mCRC patients has been reported [41]. A recent study suggests that patients with mutations in KRAS codon 12 present a significant survival advantage compared to wild-type patients treated with irinotecan-based therapy [54].…”

“…Regarding standard chemotherapy response, their potential use as predictive biomarkers is not well-established. Some articles have suggested a potential role of these mutations in standard chemotherapy response [41,42], while others have refused it [17,43]. Recently, a novel role of tumor location in the outcome of patients has been described.…”

Targeted Sequencing of Circulating Tumor DNA to Monitor Genetic Variants and Therapeutic Response in Metastatic Colorectal Cancer

“…Mutations of genes such as TP53, KRAS, NRAS, BRAF, and PIK3CA have implications for the outcome of targeted therapy and chemotherapy (18,(32)(33)(34)(35)(36)(37), and the analysis of KRAS, NRAS, and BRAF mutations is recommended in the NCCN guidelines to guide cetuximab treatment. In our cohort, all 21 patients with detectable ctDNA variants in pretreatment samples harbored at least one variant in the therapeutically relevant genes TP53, KRAS, BRAF, and PIK3CA.…”

Significance of KRAS, NRAS, BRAF and PIK3CA mutations in metastatic colorectal cancer patients receiving Bevacizumab: a single institution experience

“…Also they have been investigated as potential predictive markers of the response to bevacizumab or oxaliplatin, but results are controversial (8,9,(15)(16)(17).…”