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EGFR-TKI monotherapy versus combination therapy as first-line treatment for EGFR-mutant NSCLC with brain metastases:
Fei Qi1,2, Yuzhu Chen1, Yi Han3
1Medical Oncology Department, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, P.R. China.
Background:
Optimal first-line treatment for epidermal growth factor receptor (EGFR) mutant NSCLC with brain metastases (BMs) has not been fully defined. We aimed to compare different first-line tyrosine kinase inhibitor (TKI) combination therapies and monotherapy for these patients in a real-world setting, especially in the era of 3rd generation TKIs.
Methods:
Patients with EGFR-mutant NSCLC and BMs receiving first-line EGFR-TKIs from 2019 to 2023 were retrospectively reviewed (n = 150): TKI alone (n = 73), TKI plus brain radiation (TKI + BRT, n = 25), TKI plus bevacizumab (TKI + BEV, n = 38) and TKI plus chemotherapy (TKI + CT, n = 14). Intracranial progression-free survival (iPFS), PFS, overall survival (OS), responses and adverse events of each group were compared and survival beneficial population were explored.
Results:
Among enrolled patients, majority (70.7%) received 3rd generation EGFR-TKIs and 29.3% received 1st /2nd generation drugs. The median iPFS of TKI alone group was significantly inferior than those in TKI + BRT, TKI + BEV and TKI + CT groups (22.1 vs. 32.9 months vs. not reached [NR] vs. NR, p = 0.001). The median PFS and OS were 11.1 and 40.1 months, 18.9 and 67.1 months, 16.5 and 38.8 months, 39.8 and 79.8 months, respectively, with TKI alone, TKI + BRT, TKI + BEV and TKI + CT (PFS, p = 0.014; OS, p = 0.015). The combination therapies brought iPFS and PFS benefits over TKI alone regardless of TKI generations. A linear correlation was demonstrated between iPFS and OS (R2 = 0.508, p < 0.001). Multivariate analysis revealed that the addition of BRT (HR = 0.375, 95%CI, 0.176-0.802, p = 0.011) or bevacizumab (HR = 0.294, 95%CI, 0.141-0.611, p = 0.001) significantly reduced intracranial progression risk. Whereas, the combinations of TKI and RT (HR = 0.326, 95%CI, 0.128-0.834, p = 0.019) or chemotherapy (HR = 0.083, 95%CI, 0.010-0.666, p = 0.019) were independent factors for favorable OS. No significant difference on survival or toxicity was observed among the three combination therapies.
Conclusion:
EGFR-TKI combination therapies improved iPFS, PFS and OS than TKI monotherapy for patients with EGFR-mutant NSCLC and BMs irrespective of TKI generation or combination strategy.
Insights
First-line tyrosine kinase inhibitor (TKI) combination therapies significantly improved outcomes for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases (BMs) compared to TKI monotherapy. Combination strategies enhance intracranial progression-free survival (iPFS) and overall survival (OS).
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Optimal first-line treatment for EGFR-mutant NSCLC with brain metastases (BMs) remains undefined.
- Real-world data is crucial for comparing tyrosine kinase inhibitor (TKI) combination therapies and monotherapy in this patient population, especially with the advent of third-generation TKIs.
Purpose of the Study:
- To compare the efficacy of different first-line TKI combination therapies versus monotherapy in patients with EGFR-mutant NSCLC and BMs.
- To evaluate intracranial progression-free survival (iPFS), progression-free survival (PFS), and overall survival (OS) across various treatment strategies.
- To identify factors associated with improved survival benefits in this patient cohort.
Main Methods:
- Retrospective review of 150 patients with EGFR-mutant NSCLC and BMs receiving first-line EGFR-TKIs between 2019 and 2023.
- Treatment groups included: TKI alone, TKI plus brain radiation (TKI+BRT), TKI plus bevacizumab (TKI+BEV), and TKI plus chemotherapy (TKI+CT).
- Comparison of iPFS, PFS, OS, response rates, and adverse events; survival beneficial populations were explored.
Main Results:
- Majority of patients (70.7%) received third-generation EGFR-TKIs.
- Combination therapies (TKI+BRT, TKI+BEV, TKI+CT) demonstrated significantly superior median iPFS compared to TKI alone (22.1 months vs. not reached).
- Median PFS and OS were significantly longer for combination therapies versus TKI alone, with TKI+CT showing the longest median OS (79.8 months). Addition of BRT or bevacizumab significantly reduced intracranial progression risk, while TKI+RT or TKI+CT were independent factors for favorable OS.
Conclusions:
- First-line EGFR-TKI combination therapies significantly improve iPFS, PFS, and OS compared to TKI monotherapy in patients with EGFR-mutant NSCLC and BMs.
- These benefits are observed irrespective of TKI generation or the specific combination strategy employed.
- Combination therapies represent a superior treatment approach for managing NSCLC with brain metastases.
