KRAS mutations are found in 20-30 % of non-small cell lung cancers (NSCLC) and were traditionally considered undruggable. KRAS mutation confers sensitivity to KRAS covalent inhibitors, however its prognostic impact remains unclear. This study assesses the frequency, clinical features, prevalence of brain metastases and outcomes in KRAS NSCLC in a real-world setting.
Patients enrolled in the prospective Thoracic Malignancies Cohort (TMC) between July 2012 to October 2019 with recurrent/metastatic non-squamous NSCLC, available KRAS results, and without EGFR/ALK/ROS1 gene aberrations, were selected. Data was extracted from TMC and patient records. Clinicopathologic features, treatment and overall survival (OS) was compared for KRAS wildtype (KRAS) and KRAS mutated (KRAS); and KRAS and other (KRAS) mutations.
Of 1386 NSCLC patients, 1040 were excluded: non-metastatic/recurrent (526); unknown KRAS status (356); ALK/EGFR/ROS1 positive (154); duplicate (4). Of 346 patients analysed, 144 (42 %) were KRAS, of whom 65 (45 %) were KRAS. All patients with KRAS were active or ex-smokers, compared to 92 % of KRAS and 83 % of KRAS. The prevalence of brain metastases during follow-up was similar between KRAS and KRAS (33 % vs 40 %, p = 0.17), and KRAS and KRAS (40 % vs 41 %, p = 0.74). The proportion of patients receiving one or multiple lines of systemic therapy was comparable. OS was similar between KRAS and KRAS (p = 0.54), and KRAS and KRAS (p = 0.39).
Patients with KRAS and KRAS, and KRAS and KRAS NSCLC have comparable clinical features, treatment and survival. While not prognostic, KRAS may be an important predictive biomarker as promising KRAS covalent inhibitors continue to be developed.

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