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Published on: November 22, 2021
Optimal first-line treatment for EGFR-mutated NSCLC: a comparative analysis of osimertinib and second-generation
Hsu-Yuan Chen1,2, Chia-Hung Chen1,2, Wei-Chih Liao1,2
1Department of Internal Medicine, Division of Pulmonary and Critical Care, China Medical University Hospital, Taichung, Taiwan.
Background:
Osimertinib is an irreversible third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). It is the preferred first-line treatment for EGFR-mutated non-small cell lung cancer (NSCLC) compared to first-generation EGFR-TKIs. However, limited research has compared its clinical effectiveness with second-generation (2nd G) EGFR-TKIs.
Materials And Methods:
This study recruited patients diagnosed with stage IIIb-IV EGFR-mutated NSCLC who received first-line treatment with either 2nd G EGFR-TKIs (afatinib and dacomitinib) or osimertinib between April 2020 and April 2023.
Results:
The final analysis included 168 patients, of whom 113 received 2nd G EGFR-TKIs (afatinib or dacomitinib) and 55 received osimertinib. The median progression-free survival (PFS) did not differ significantly between 2nd G EGFR-TKIs and osimertinib (del 19: 17.6 months; L858R: 20.0 months vs. 28.3 months, p = 0.081). In patients with the EGFR exon 19 deletion, osimertinib conferred a longer median PFS (28.3 vs. 17.6 months, p = 0.118) and time to treatment failure (30.2 vs. 22.7 months, p = 0.722) than 2nd G EGFR-TKIs. However, the differences were not statistically significant. In patients with with the EGFR exon 19 deletion and central nervous system metastasis, the median PFS did not differ significantly between those treated with osimertinib (14.3 months) and those treated with 2nd G EGFR-TKIs (17.6 months; p = 0.881). Multivariate regression analysis revealed that the NSCLC stage was the only independent negative predictor of PFS. The treatment patterns in the second line also differed significantly between groups (p = 0.008).
Conclusions:
This study found comparable effectiveness between osimertinib and 2nd G EGFR-TKIs as first-line treatment for advanced EGFR-mutated NSCLC, with only the NSCLC stage identified as a negative predictor of PFS. However, whether the different second-line treatments affect overall survival should be examined.
Insights
Osimertinib and second-generation EGFR-TKIs show similar effectiveness for advanced EGFR-mutated non-small cell lung cancer (NSCLC). NSCLC stage is the key predictor of progression-free survival in first-line treatment.
Area of Science:
- Oncology
- Pharmacology
- Clinical Research
Background:
- Osimertinib is a preferred first-line treatment for EGFR-mutated non-small cell lung cancer (NSCLC).
- Limited data exists comparing osimertinib with second-generation (2nd G) EGFR-TKIs in the first-line setting.
- This study addresses this gap by comparing clinical outcomes.
Purpose of the Study:
- To compare the clinical effectiveness of osimertinib versus 2nd G EGFR-TKIs (afatinib and dacomitinib) as first-line treatment.
- To identify predictors of progression-free survival (PFS) in patients with EGFR-mutated NSCLC.
Main Methods:
- Retrospective study of 168 patients with stage IIIb-IV EGFR-mutated NSCLC.
- Patients received either 2nd G EGFR-TKIs or osimertinib as first-line therapy.
- Progression-free survival (PFS) and time to treatment failure were analyzed.
Main Results:
- No significant difference in median PFS between osimertinib and 2nd G EGFR-TKIs (17.6-20.0 months vs. 28.3 months).
- Osimertinib showed a trend towards longer PFS in EGFR exon 19 deletion patients, but not statistically significant.
- NSCLC stage was the only independent negative predictor of PFS; second-line treatment patterns differed significantly.
Conclusions:
- Osimertinib and 2nd G EGFR-TKIs demonstrate comparable effectiveness as first-line treatment for advanced EGFR-mutated NSCLC.
- NSCLC stage is a critical factor influencing PFS.
- Further research is needed to assess the impact of different second-line treatments on overall survival.
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