Journal Article

DKFZ-2026-02694

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dose-Dependent Intracranial Response to Sotorasib in KRASG12C-Mutated Lung Cancer Brain Metastases: A Case Report.

Hoersting, N.DKFZ* ; Hense, J.DKFZ* ; Schuler, M.DKFZ* ; Guberina, N.DKFZ* ; Guberina, M.DKFZ* ; Opitz, M. ; Wiesweg, M.DKFZ*

2026
Karger Basel

Abstract: 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.

Keyword(s): Humans (MeSH) ; Female (MeSH) ; Brain Neoplasms: secondary (MeSH) ; Brain Neoplasms: drug therapy (MeSH) ; Brain Neoplasms: genetics (MeSH) ; Lung Neoplasms: drug therapy (MeSH) ; Lung Neoplasms: genetics (MeSH) ; Lung Neoplasms: pathology (MeSH) ; Proto-Oncogene Proteins p21(ras): genetics (MeSH) ; Mutation (MeSH) ; Treatment Outcome (MeSH) ; Dose-Response Relationship, Drug (MeSH) ; Piperazines: administration & dosage (MeSH) ; Adenocarcinoma of Lung: drug therapy (MeSH) ; Adenocarcinoma of Lung: genetics (MeSH) ; Adenocarcinoma: drug therapy (MeSH) ; Adenocarcinoma: genetics (MeSH) ; Antineoplastic Agents: administration & dosage (MeSH) ; Middle Aged (MeSH) ; Brain metastases ; Case report ; Intracranial response ; KRASG12C ; Sotorasib ; Proto-Oncogene Proteins p21(ras) ; KRAS protein, human ; Piperazines ; Antineoplastic Agents

Note: #NCTZFB9#

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Contributing Institute(s):

1. Koordinierungsstelle NCT West (WT01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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