Lung cancer (Amsterdam, Netherlands) · 2025
Evaluating docetaxel effectiveness in KRAS G12C-mutated NSCLC: insights from a Real-World cohort.
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Scheffler Matthias, Tzala Lia, Louie Karly, Persigehl Thorsten, Lennartz Simon, Öhrling Katarina, Gehrman Julia, Ruge Lea, John Felix, Rasokat Anna, Kron Anna, Potzner Michaela, Merkelbach-Bruse Sabine, Buettner Reinhard, Siebolts Udo, Wolf Jürgen
Аннотация
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.
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.