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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Real-World Treatment Patterns and Effectiveness of Targeted and Immune Checkpoint Inhibitor-Based Systemic Therapy in
Amanda J W Gibson1, Aliyah Pabani1,2, Michelle L Dean1
1Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Introduction:
BRAF mutations (present in 2%-3% of NSCLC) are a known oncogenic driver and emerging therapeutic target. There is a scarcity of real-world data describing the clinical characteristics, treatment patterns, and effectiveness of targeted BRAF-inhibiting and immune checkpoint inhibitor (ICI)-based systemic therapies, yet this is required for appropriate treatment decisions that optimize patient outcome.
Methods:
Demographic, clinical, treatment, and outcome data of patients with BRAF mutation-positive NSCLC diagnosed between 2018 and 2022 were identified from the Glans-Look Lung Cancer Research database and included in this analysis.
Results:
A total of 53 BRAF mutation-positive patients were identified (V600E, n = 35; non-V600E, n = 18). Furthermore, 46 patients (87%) were diagnosed with metastatic disease, of whom 61% were treated with systemic anticancer therapy, which significantly improved overall survival (34.1 versus 2.2 mo, p = 0.01). ICI-based regimens were found to have effectiveness in the first-line setting for both V600E and non-V600E cohorts (objective response rate: 38%-43%; real-world calculations of median progression-free survival: 10.5-10.8 mo, respectively). Dual-targeted BRAF/MEK inhibition was also found to have effectiveness in the first-line setting for V600E patients (objective response rate: 33%, real-world calculations of median progression-free survival: 15.2 mo).
Conclusions:
This study of real-world patients with BRAF mutations confirms the importance of effective systemic therapies. Both dual-targeted BRAF/MEK inhibition and ICI-based regimens have evidence of benefit in this population revealing that real-world populations can experience similar clinical response and outcome to clinical trial cohorts on these treatment regimens. Future studies to clarify the role of co-mutations on response to both dual-targeted BRAF/MEK inhibition and ICI-based regimens may be important to treatment selection and optimization of patient outcome.
Insights
Targeted therapies and immune checkpoint inhibitors (ICIs) show significant survival benefits for patients with BRAF-mutated non-small cell lung cancer (NSCLC). Real-world data confirm these treatments improve outcomes in both V600E and non-V600E BRAF-mutated NSCLC.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- BRAF mutations are oncogenic drivers in 2-3% of non-small cell lung cancer (NSCLC) cases.
- Targeted BRAF inhibitors and immune checkpoint inhibitors (ICIs) are emerging therapies for BRAF-mutated NSCLC.
- Limited real-world data exist on the effectiveness of these systemic therapies in diverse patient populations.
Purpose of the Study:
- To analyze real-world clinical characteristics, treatment patterns, and outcomes for patients with BRAF-mutated NSCLC.
- To evaluate the effectiveness of targeted BRAF-inhibiting and ICI-based therapies in this patient group.
- To compare outcomes between BRAF V600E and non-V600E mutations.
Main Methods:
- Retrospective analysis of demographic, clinical, treatment, and outcome data.
- Inclusion of patients with BRAF-mutated NSCLC diagnosed between 2018 and 2022.
- Data sourced from the Glans-Look Lung Cancer Research database.
Main Results:
- 53 BRAF-mutated NSCLC patients identified (35 V600E, 18 non-V600E).
- Systemic therapy significantly improved overall survival (34.1 vs. 2.2 months, p=0.01) in metastatic patients.
- ICI regimens showed effectiveness in first-line settings for both V600E and non-V600E cohorts (ORR: 38-43%, mPFS: 10.5-10.8 months).
- Dual BRAF/MEK inhibition demonstrated effectiveness in V600E patients (ORR: 33%, mPFS: 15.2 months).
Conclusions:
- Real-world data support the efficacy of systemic therapies for BRAF-mutated NSCLC.
- Both dual BRAF/MEK inhibition and ICI-based regimens offer clinical benefits.
- Future research should explore the impact of co-mutations on treatment response and patient outcomes.
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