The most common of the KRAS mutations in non-small cell lung cancer (NSCLC) has been flagged as potentially targetable and may therefore help improve patient outcomes.
A real-world study from the Thoracic Malignancies Cohort at Peter MacCallum Cancer Centre comprised 346 patients with metastatic or recurrent non-squamous NSCLC who had available KRAS mutation test results and did not have an EGFR, ALK, or ROS1 gene aberration.
The study found 58% of patients were KRASWT. Of the remaining patients with KRAS mutations, 45% had a KRASG12C and 55% had one of nine other KRAS mutations or codon 13.
The study, led by Dr Wanda Cui, found all patients with KRASG12C mutant NSCLC were current or former smokers.
“We usually associate oncogenic driven NSCLC (eg EGFR, ALK and ROS1) with never or light ex smokers,” Dr Cui told the limbic.
“Therefore this finding is important as we need to comprehensively sequence all NSCLC, not just non smokers, given KRASG12C is an important target in smokers.”
The study also found that patients with KRASG12C mutations had a higher frequency of brain metastases at diagnosis (28%) compared to KRASWT (17 %) and KRASother (19 % ) although this difference was not statistically significant.
“Brain mets are common and thus current / future drug development should focus on improved intracranial activity as seen with 2nd/3rd generation EGFR and ALK inhibitors,” Dr Cui said.
There were no other significant differences in clinicopathologic characteristics or in survival between KRASmut and KRASWT patients, or KRASG12C versus KRASother patients.