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Real-World Outcomes in BRAF-Mutant Non-small Cell Lung Cancer: A Multicenter Analysis From the Turkish Oncology Group
Tuğba Akın Telli1, Ali Murat Tatlı2, Özkan Alan3
1Division of Medical Oncology, Demiroğlu Bilim University Faculty of Medicine, Florence Nightingale Hospital, Istanbul, Turkey.
Background:
Real-world data on BRAF-mutant non-small cell lung cancer (NSCLC) remain limited, particularly regarding outcomes with dabrafenib plus trametinib (D + T).
Methods:
This multicenter retrospective study included 88 patients with advanced BRAF-mutant NSCLC treated across 30 centers. Clinicopathologic characteristics, treatment outcomes, and safety data were collected and analyzed. Patients received either chemotherapy or dabrafenib plus trametinib in the first-line or subsequent settings. Progression-free survival (PFS), overall survival (OS), and objective response rates (ORR) were compared across treatment groups.
Results:
Among 88 patients (78 V600E, 10 non-V600E), median age was 64 years. Co-mutations were more frequent in non-V600E cases (40% vs. 10%). Brain metastases were more frequent in non-V600E cases (60% vs. 15%, p = .001). First-line D + T was associated with superior ORR (67% vs. 39%, p = .02), DCR (81% vs. 51%, p = .009), and PFS (median 13.1 vs. 6.1 months, p = .007) compared to chemotherapy, while OS was similar between groups. Among chemotherapy regimens, platinum-pemetrexed outperformed platinum-taxane in terms of ORR (77% vs. 33%, p = .006) and PFS (median 14.7 vs. 3.2 months, p = .002). No significant differences in efficacy were observed between first-line and later-line use of D + T. Co-mutations were associated with shorter OS (median 8.7 vs. 20.2 months, p = .009). PD-L1 status and BRAF subtype did not impact OS. Median treatment duration with D + T was 10.6 months, with treatment-related adverse events occurring in 61% of patients, most commonly fatigue and pyrexia.
Conclusions:
In this real-world cohort, dabrafenib plus trametinib was associated with superior response rates and PFS compared to chemotherapy in the first-line setting. Presence of co-mutations was associated with poorer outcomes.
Insights
Dabrafenib plus trametinib (D + T) showed superior response rates and progression-free survival (PFS) compared to chemotherapy in the first-line treatment of BRAF-mutant non-small cell lung cancer (NSCLC). Co-mutations were linked to worse outcomes in this real-world study.
Area of Science:
- Oncology
- Medical Research
Background:
- Limited real-world data exist for BRAF-mutant non-small cell lung cancer (NSCLC) outcomes.
- Specific data on dabrafenib plus trametinib (D + T) in this population are scarce.
Purpose of the Study:
- To evaluate the real-world effectiveness of dabrafenib plus trametinib (D + T) versus chemotherapy.
- To analyze outcomes in patients with BRAF-mutant NSCLC.
Main Methods:
- A multicenter retrospective study of 88 patients with advanced BRAF-mutant NSCLC.
- Comparison of clinicopathologic characteristics, treatment outcomes (PFS, OS, ORR), and safety.
- Analysis of first-line and subsequent treatment settings.
Main Results:
- First-line D + T demonstrated superior objective response rates (ORR) and progression-free survival (PFS) compared to chemotherapy.
- Platinum-pemetrexed showed better ORR and PFS than platinum-taxane chemotherapy.
- Co-mutations were associated with shorter overall survival (OS).
Conclusions:
- Dabrafenib plus trametinib (D + T) offers improved response rates and PFS over chemotherapy in first-line BRAF-mutant NSCLC.
- Co-mutations negatively impact outcomes in this patient group.
