Dados do Trabalho

Título

PREVALENCE AND MOLECULAR PROFILE OF KRAS MUTATION IN PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER FROM AN ONCOLOGY REFERENCE CENTER IN SOUTH OF BRAZIL

Introdução

Kirsten-Rat Sarcoma (KRAS) is the most commonly mutated gene found in non-small cell lung cancer (NSCLC), occurring in approximately 30% of NSCLC with adenocarcinoma histology. The mutated form of KRAS protein (mKRAS) is a poor prognostic factor and an important therapeutic target due to its high prevalence. In Brazil, there are few clinical data on KRAS mutation profile in lung cancer.

Objetivo

To determine the molecular profile of the KRAS gene in patients with advanced NSCLC and correlate with clinical factors to assess their impact on overall survival.

Método

In this retrospective observational study, from October 2016 to March 2021, we reviewed medical records of patients with non-squamous NSCLC treated at an Oncology Center in Florianópolis/SC who had their tumor samples submitted to a next-generation sequencing (NGS) panel that tested for KRAS, NRAS, BRAF and EGFR mutations. Clinical data reported here consists of age, sex, histological subtype and smoking status. Quantitative data were compared with Mann-Whitney test, qualitative data were compared with Fisher’s exact tests and Kaplan-Meier curves with log-rank test were used to compare overall survival.

Resultado

A total of 186 samples were sent for biomarker analysis, 182 could be analyzed (98%). Adenocarcinoma was the predominant histological subtype regardless of the presence of mutation (97%). The KRAS gene mutation was present in 45 samples (24.2%), followed by 38 (20,4%) EGFR mutations, 5 (2,75%) BRAF mutations and 2 (1,09%) NRAS mutations. G12C was the most commonly mutation detected (n=15, 33,3%), succeeded by G12V (n=9, 20%) and G12D (n=8, 17,8%). The median age was 66 years (range 54-79) among patients with mKRAS and 63 years (range 28-89) among patients with wild-type (wt) KRAS (p = 0.079). Among the mKRAS patients, 53,3% were women vs 47% among the wtKRAS (p = 0.46). Only 1 (2,4%) mKRAS patient was a never smoker compared to 23 (19%) do wtKRAS patients (p<0,0001). The median overall survival of mKRAS and wtKRAS patients was 11.7 (95% CI 4.6-18.7) and 11,8 months (95% CI 92,7-14,3) respectively (p = 0.42).

Conclusão

The KRAS mutation was identified in almost 25% of patients and G12C mutation was the most frequent, which is extremely relevant due to its therapeutic potential. There is a strong relationship between smoking status and the presence of KRAS mutation. These findings acknowledge the importance of evaluating the KRAS mutation in non-squamous NSCLC.

Palavras-chave

KRAS, non-small cell lung cancer, targeted therapy