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Updated: Oct 9, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Front-Line Therapy in EGFR Exon 19 Deletion and 21 Leu858Arg Mutations in Advanced Non-Small Cell Lung Cancer: A
Tongji Xie1, Zihua Zou1, Chengcheng Liu2
1National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Objective:
This study aimed to compare the efficacy of different first-line strategies based on different EGFR mutation types (19 deletion and 21 Leu858Arg mutations).
Methods:
We conducted a systematic review and network meta-analysis (NMA) by searching and analyzing RCTs on PubMed, Embase, Cochrane Library, ASCO.org, and ESMO.org, from inception to September 30th, 2020.
Results:
Nineteen RCTs involving 5450 patients were finally included in this study, covering 10 different treatment strategies. The Bayesian ranking results suggested that, in terms of PFS, in the overall population and in patients with 19del mutation, osimertinib was most likely to rank the first, with the cumulative probabilities of 41.89% and 45.73%, respectively, while for patients with 21 Leu858Arg mutation, standard of care (SoC, represents first-generation EGFR-TKIs in this NMA) + chemotherapy was most likely to rank the first, with the cumulative probabilities of 30.81% in PFS. Moreover, SoC + chemotherapy provided the best overall survival benefit for the overall population and patients with 19del, with the cumulative probabilities of 57.85% and 33.51%, respectively. In contrast, for patients with 21 Leu858Arg mutation, dacomitinib showed the most favorable overall survival, with the cumulative probabilities of 36.73%.
Conclusions:
In this NMA, osimertinib and SoC combined with chemotherapy would be the optimal first-line treatment options for advanced NSCLC patients harboring EGFR 19 deletion mutation and 21 Leu858Arg mutation, respectively. This finding is likely to be adopted in clinical practice and provide guidance for future clinical study design. Systematic review registration: INPLASY2020100059.
Insights
Osimertinib is the top first-line treatment for EGFR 19 deletion NSCLC, while standard of care chemotherapy is best for 21 L858R mutations. This network meta-analysis guides optimal treatment strategies for advanced non-small cell lung cancer.
Area of Science:
- Oncology
- Genomics
- Pharmacology
Background:
- Epidermal Growth Factor Receptor (EGFR) mutations are key drivers in non-small cell lung cancer (NSCLC).
- First-line treatment efficacy varies significantly based on specific EGFR mutation subtypes, including 19 deletion and 21 L858R.
Purpose of the Study:
- To compare the effectiveness of various first-line treatment strategies for advanced NSCLC.
- To analyze efficacy based on distinct EGFR mutation types: 19 deletion and 21 L858R.
Main Methods:
- A systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs).
- Searched major databases (PubMed, Embase, Cochrane Library) and oncology society websites (ASCO, ESMO) up to September 2020.
- Included 19 RCTs with 5450 patients, evaluating 10 different treatment strategies.
Main Results:
- For progression-free survival (PFS), osimertinib ranked first for overall population (41.89%) and 19del mutation patients (45.73%).
- For 21 L858R mutation patients, standard of care (SoC) chemotherapy showed the highest PFS probability (30.81%).
- SoC chemotherapy offered the best overall survival for the overall population (57.85%) and 19del patients (33.51%), while dacomitinib was superior for 21 L858R patients (36.73%).
Conclusions:
- Osimertinib is recommended as the optimal first-line treatment for advanced NSCLC with EGFR 19 deletion mutations.
- Standard of care chemotherapy is the preferred first-line option for advanced NSCLC with EGFR 21 L858R mutations.
- Findings provide evidence-based guidance for clinical practice and future research in EGFR-mutated NSCLC.
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