Case Report: Dose dependent intracranial response to sotorasib in KRASG12C-mutated lung cancer brain metastases

KRASG12C inhibitors such as sotorasib have expanded precision-oncology options for non-small cell lung cancer (NSCLC). However, central nervous system (CNS) disease control remains a major clinical challenge. We report the case of a female patient with extensively pretreated KRASG12C-mutated lung adenocarcinoma and metachronous progressive brain metastases. Initially, peripheral and cerebral lesions responded to once daily sotorasib 960 mg (standard dose). Following cerebral progression, tolerance-adapted escalation to 1,920 mg achieved renewed intracranial disease control. In conclusion, this case illustrates that tolerance-adapted dose escalation may offer a meaningful therapeutic option for selected patients experiencing CNS progression under standard dosing.