Trametinib as second-line therapy for advanced KRAS G12C-mutant non-small cell lung cancer: a single-center clinical analysis of 20 cases

To investigate the clinical efficacy and safety of the MEK1/2 inhibitor trametinib in the second-line treatment of advanced non-small cell lung cancer (NSCLC) with a KRAS G12C mutation and to explore potential clinical factors associated with treatment response.

A retrospective analysis was performed on 20 patients with advanced NSCLC harboring the KRAS G12C mutation who were admitted to Heping Hospital, which is affiliated with Changzhi Medical College, from January 2020 to June 2023. After disease progression following first-line platinum-based doublet chemotherapy combined with PD-1/PD-L1 inhibitor therapy, all patients received 2 mg of trametinib orally once daily, with 21 days defined as one treatment cycle, until disease progression, death, or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR), and the secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse reactions.

Among the 20 patients, 16 were male, and 4 were female, with a median age of 65 years (range 51-78 years); 18 patients had a history of smoking, and the predominant histological type was adenocarcinoma (19 cases). The ORR was 27.8% (5/18), and the DCR was 72.2% (13/18). The median follow-up duration was 10.2 months, the median PFS was 3.8 months (95% CI: 2.9-4.7 months), and the median OS was 8.6 months (95% CI: 6.4-10.8 months). Univariate analysis indicated that the ORR of patients without bone metastasis was significantly greater than that of patients with bone metastasis (35.7% vs. 0%, P = 0.042). The DCR was greater in patients with PD-L1 expression ≥1% (81.8% vs. 50.0%, P = 0.039). The most common treatment-related adverse reactions in the overall cohort were rash (35.0%), diarrhea (25.0%), and fatigue (20.0%). The incidence of grade 3 adverse reactions was 15.0%. No grade 4 or higher adverse reactions or treatment-related deaths were observed.

Trametinib, as a second-line treatment for advanced NSCLC with a KRAS G12C mutation, has demonstrated evident anti-tumor activity, manageable toxicity, and favorable tolerability; exploratory analysis indicated that the absence of bone metastasis and PD-L1 positivity might be associated with improved outcomes. This regimen is highly clinically accessible and may serve as a second-line treatment option when KRAS G12C-specific inhibitors are unavailable. Its clinical value requires further validation through large-sample prospective studies.