Evaluating docetaxel effectiveness in KRAS G12C-mutated NSCLC: insights from a Real-World cohort
Menée dans un contexte de vie réelle à partir de données 2015-2019 portant sur des patients atteints d'un cancer du poumon non à petites cellules et présentant la mutation G12C au niveau du gène KRAS, cette étude évalue l'efficacité, du point de vue de la survie globale et de la survie sans progression, du docétaxel seul et en combinaison
Background: Specific KRAS G12C inhibitors have reached the stage of targeted therapy for non-small cell lung cancer (NSCLC). However, there is a dearth of real-world data in the context of immune checkpoint blockade and docetaxel effectiveness in NSCLC patients with KRAS G12C mutations. This study was designed to address this gap in knowledge by analyzing a real-world cohort of patients with KRAS G12C mutations treated with docetaxel in the era of immune-checkpoint-blockade availability.
Patients and Methods: The Network Genomic Medicine (NGM) database was queried to identify patients with KRAS G12C mutations who had been treated with docetaxel monotherapy or combinations between July 1st, 2015, and December 31st, 2019.
Results: The median rwOS was 7.6 months (95 % CI: 6.5–14.5), with improved outcomes observed for docetaxel plus nintedanib (10.4 months) compared to docetaxel monotherapy (6.5 months). The rwPFS was 3.4 months overall, with combination therapy showing marginally superior efficacy (4.3 vs. 2.2 months). The presence of concomitant mutations in STK11 and KEAP1 was associated with inferior outcomes, whereas elevated PD-L1 expression was associated with enhanced rwOS. Notably, the inclusion of patients with ECOG 2 or higher underscored the unfavorable outcomes observed in this subgroup, which is typically excluded from pivotal trials.
Conclusion: The effectiveness of docetaxel, administered with or without antiangiogenic agents, was found to be limited in a real-world setting of non-small cell lung cancer (NSCLC) patients with a KRAS G12C mutation, emphasizing the need for novel therapies. Comprehensive molecular profiling remains crucial for optimizing treatment outcomes in this heterogeneous subgroup.
Lung Cancer , résumé, 2025