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Comparing the Effectiveness and Safety of First-line Interventions in Patients With Advanced Epidermal Growth Factor
1Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, China; Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Aims:
This network meta-analysis (NMA) aimed to identify the most effective first-line intervention (FLI) for advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), particularly in patients with varying brain metastasis (BM) status.
Materials And Methods:
Data were collected from randomized controlled trials (RCTs) evaluating first-line EGFR-tyrosine kinase inhibitors (EGFR-TKIs), either alone or in combination, for EGFR-mutated advanced NSCLC (EMAN) patients. The sources included EMBASE, Web of Science, Cochrane Library, PubMed, and relevant conference abstracts from inception until December 2023.
Results:
A total of 37 RCTs, encompassing 24 intervention options, were included in the NMA. Osimertinib combined with chemotherapy (CT) significantly improved progression-free survival (PFS) compared to aumolertinib (HR, 0.61; 95% CI, 0.40-0.93), furmonertinib (HR, 0.64; 95% CI, 0.41-0.98), lazertinib (HR, 0.64; 95% CI, 0.41-0.98), osimertinib alone (HR, 0.62; 95% CI, 0.48-0.80), osimertinib + bevacizumab (HR, 0.72; 95% CI, 0.51-1.00), befotertinib (HR, 0.57; 95% CI, 0.36-0.90), and zorifertinib (HR, 0.61; 95% CI, 0.39-0.93). Further, amivantamab + lazertinib showed slightly better PFS compared to aumolertinib, furmonertinib, zorifertinib, and osimertinib + bevacizumab (HR <1, but P >0.05). Regarding overall survival (OS), amivantamab + lazertinib demonstrated superior results relative to furmonertinib (HR, 0.54; 95% CI, 0.30-0.95) and befotertinib (HR, 0.43; 95% CI, 0.24-0.77). No significant OS differences were observed among osimertinib, osimertinib + bevacizumab, osimertinib + CT, lazertinib, and amivantamab + lazertinib. In BM patients, osimertinib + CT significantly enhanced PFS compared to osimertinib (HR, 0.47; 95% CI, 0.33-0.66), furmonertinib (HR, 0.44; 95% CI, 0.21-0.90), befotertinib (HR, 0.45; 95% CI, 0.21-1.00), and zorifertinib (HR, 0.47; 95% CI, 0.25-0.89). However, no noticeable PFS differences were observed between osimertinib + CT and amivantamab + lazertinib or aumolertinib. Lastly, osimertinib + CT and zorifertinib were associated with higher rates of all-grade adverse events (AEs) and grade ≥3 AEs, respectively.
Conclusions:
In EMAN patients, osimertinib + CT and amivantamab + lazertinib were associated with optimal PFS and OS, respectively. Among BM patients, osimertinib + CT offered the best PFS benefits. These findings may assist in clinical decision-making and personalized care for EMAN and BM patients. The study is registered on PROSPERO (CRD42024506995).
Insights
Osimertinib plus chemotherapy (CT) and amivantamab plus lazertinib show optimal progression-free survival (PFS) and overall survival (OS) for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Osimertinib plus CT is best for brain metastasis (BM) patients.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) requires effective first-line interventions (FLI).
- Brain metastases (BM) are a common complication in EGFR-mutated NSCLC, impacting treatment efficacy and patient outcomes.
- Identifying optimal FLI strategies, especially for patients with BM, is crucial for improving survival and quality of life.
Purpose of the Study:
- To conduct a network meta-analysis (NMA) comparing various first-line EGFR-tyrosine kinase inhibitors (EGFR-TKIs) for advanced EGFR-mutated NSCLC.
- To evaluate the efficacy of these interventions, considering different brain metastasis (BM) statuses.
- To identify the most effective FLI for patients with EGFR-mutated advanced NSCLC, including those with BM.
Main Methods:
- Systematic literature search of randomized controlled trials (RCTs) evaluating first-line EGFR-TKIs in EGFR-mutated advanced NSCLC.
- Inclusion of data from EMBASE, Web of Science, Cochrane Library, PubMed, and conference abstracts up to December 2023.
- Network meta-analysis (NMA) of 37 RCTs with 24 intervention options to compare progression-free survival (PFS) and overall survival (OS).
Main Results:
- Osimertinib plus chemotherapy (CT) significantly improved PFS compared to several other EGFR-TKIs and monotherapy.
- Amivantamab plus lazertinib showed superior overall survival (OS) compared to furmonertinib and befotertinib.
- In patients with brain metastases (BM), osimertinib plus CT significantly enhanced PFS compared to several other treatments.
Conclusions:
- Osimertinib plus CT and amivantamab plus lazertinib are associated with optimal PFS and OS, respectively, in advanced EGFR-mutated NSCLC.
- Osimertinib plus CT provides the best PFS benefits for patients with BM.
- Findings support personalized treatment decisions for advanced EGFR-mutated NSCLC, particularly for patients with BM.
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