Pattern of brain metastases and survival in lung adenocarcinoma with KRAS or EFGR mutation

NSCLC with mutations of the KRAS or EGFR gene is associated with a high risk of brain metastases (BRA). There are few data on the prevalence and pattern of BRA and on survival in unselected KRAS or EGFR patients.

This real-world analysis (KOMPASS-study) included 326 NSCLC patients with stage IV adenocarcinoma and either KRAS mutation (n = 90), EGFR mutation (n = 87), or no known driver mutation (n = 149). Prevalence, number, and size of BRA, and the effect of BRA on overall survival (OS) were analyzed.

The prevalence of BRA was higher in KRAS patients (40 %) or EGFR patients (39 %) than in no-driver patients (27 %). KRAS patients and no-driver patients significantly more often had single BRA, whereas EGFR patients had multiple BRA (median number 1, 2, and 4, respectively). The presence of BRA did not adversely affect OS in KRAS patients (22.3 vs. 19.2 months, HR 0.91) and no-driver patients (8.9 vs. 10.9 months, HR 0.99). EGFR patients with BRA had inferior OS (20.5 vs. 35.5 months, HR 2.70, p = 0.0004). Patients with single BRA had improved OS (22.3 vs. 13.2 months, p = 0.013).

The lack of a negative effect of BRA on OS in KRAS patients or no-driver patients may be due to the frequent finding of a single BRA amenable to ablative treatment. The negative effect of BRA on OS in EGFR patients points to a distinct biology of EGFR-mutated NSCLC leading to a characteristic radiological pattern of multiple BRA which are not amenable to ablative treatment.