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Evaluating docetaxel effectiveness in KRAS G12C-mutated NSCLC: insights from a Real-World cohort
Matthias Scheffler1, Lia Tzala2, Karly Louie2
1Department I for Internal Medicine and Center for Integrated Oncology Aachen Bonn Cologne Dusseldorf, University of Cologne, Faculty of Medicine and University Hospital of Cologne, Lung Cancer Group Cologne, Cologne, Germany.
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.
Insights
Docetaxel effectiveness is limited for non-small cell lung cancer (NSCLC) patients with KRAS G12C mutations, even with combination therapies. Comprehensive molecular profiling is crucial for improving outcomes in this patient group.
Area of Science:
- Oncology
- Genomics
- Pharmacology
Background:
- Non-small cell lung cancer (NSCLC) treatment landscape includes targeted KRAS G12C inhibitors.
- Limited real-world data exists on docetaxel efficacy alongside immune checkpoint blockade for KRAS G12C-mutated NSCLC.
- This study addresses the knowledge gap by analyzing a real-world cohort.
Purpose of the Study:
- To evaluate the real-world effectiveness of docetaxel in patients with KRAS G12C-mutated NSCLC.
- To assess outcomes based on docetaxel monotherapy versus combination treatments.
- To identify factors influencing treatment response in this specific NSCLC subgroup.
Main Methods:
- Retrospective analysis of the Network Genomic Medicine (NGM) database.
- Inclusion of patients with KRAS G12C mutations treated with docetaxel between July 2015 and December 2019.
- Evaluation of real-world overall survival (rwOS) and progression-free survival (rwPFS).
Main Results:
- Median real-world overall survival (rwOS) was 7.6 months; docetaxel plus nintedanib showed improved outcomes (10.4 months) versus monotherapy (6.5 months).
- Real-world progression-free survival (rwPFS) was 3.4 months overall, with combination therapy marginally superior (4.3 vs. 2.2 months).
- Concomitant STK11/KEAP1 mutations correlated with worse outcomes, while elevated PD-L1 expression suggested enhanced rwOS. Patients with ECOG 2+ had unfavorable outcomes.
Conclusions:
- Docetaxel, with or without antiangiogenic agents, demonstrated limited effectiveness in real-world KRAS G12C-mutated NSCLC.
- Novel therapeutic strategies are urgently needed for this patient population.
- Comprehensive molecular profiling is essential for optimizing treatment strategies in this heterogeneous NSCLC subgroup.
