Sotorasib Shows Intracranial Benefits in KRAS G12C NSCLC with Brain Metastases
Publication Title: 58P Real-world intracranial effectiveness of sotorasib in second-line (2L) and beyond (2L+) treatment (tx) of KRAS G12C-mutated non-small cell lung cancer (NSCLC) with brain metastases (BM)
Summary
- Question
- This study examined the real-world effectiveness of sotorasib, a targeted cancer therapy, in treating brain metastases (BM) in patients with advanced non-small cell lung cancer (NSCLC) that carries a specific genetic mutation known as KRAS G12C. The researchers aimed to assess two key outcomes: overall survival (OS), which measures how long patients lived after starting treatment, and intracranial progression-free survival (iPFS), which tracks the time before brain metastases worsened or patients died.
- Why it Matters
- Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and brain metastases are a serious complication that worsen outcomes for many patients. The KRAS G12C mutation, found in a subset of NSCLC cases, has been challenging to treat effectively. Sotorasib is one of the first therapies targeting this mutation. Understanding its real-world impact on brain metastases is critical for improving treatment strategies and providing clinicians with evidence to guide care decisions. The findings are relevant to both healthcare providers and patients as they offer insights into the therapy's potential to extend survival and improve quality of life.
- Methods
- The study analyzed medical records from 135 patients with KRAS G12C-mutated NSCLC and brain metastases who began sotorasib treatment in the United States between May 2021 and February 2024. Patients were treated in either the second-line (2L) setting, meaning after one prior therapy, or later (2L+). Both previously treated and untreated brain metastases were included. Key outcomes, including overall survival and intracranial progression-free survival, were tracked for at least 12 months.
- Key Findings
- The median overall survival for patients treated with sotorasib was 9.5 months in the second-line group and 9.4 months in the broader 2L+ group. For patients with good overall health (ECOG performance status 0–1), survival was slightly higher at 11.2 and 10.5 months, respectively. Intracranial progression-free survival was 7.0 months across all groups. These results suggest that sotorasib provides consistent and clinically meaningful benefits in managing brain metastases in this patient population.
- Implications
- The findings support the use of sotorasib as an effective treatment option for patients with KRAS G12C-mutated NSCLC and brain metastases, offering survival benefits comparable to those observed in clinical trials. This reinforces the drug’s role in real-world clinical settings and provides a viable option for managing a difficult-to-treat subset of lung cancer patients.
- Next Steps
- The authors highlighted the need for further research to explore sotorasib’s effectiveness in combination with other therapies, as well as its impact on different subgroups of patients, to optimize treatment outcomes for those with KRAS G12C-mutated NSCLC and brain metastases.
- Funding Information
- This research was supported by Amgen Inc., which provided funding for the study. Yale University also provided funding and support for this research.
Full Citation
Nadal E, Sabari J, Dingemans A, Gadgeel S, Lee J, Wolf J, Ko H, Gupta R, Jassim R, Ardito-Abraham C, Frias M, Goldberg S. 58P Real-world intracranial effectiveness of sotorasib in second-line (2L) and beyond (2L+) treatment (tx) of KRAS G12C-mutated non-small cell lung cancer (NSCLC) with brain metastases (BM). ESMO Open 2026, 11: 106365. DOI: 10.1016/j.esmoop.2026.106365.
Authors
E. Nadal
First AuthorSarah Goldberg, MD, MPH
Last AuthorProfessor of Internal Medicine (Medical Oncology & Hematology)