Abstract 78P
Background
Osimertinib is highly CNS active third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that targets EGFR-TKI-sensitizing mutations and the EGFR-T790M resistance mutation. This systematic review investigates the efficacy and safety of combining chemotherapy with osimertnib in patients with EGFR-mutated advanced NSCLC.
Methods
A literature search, including grey literature, was conducted in PubMed, Scopus, Cochrane Library, and Web of Science from inception to November 2024. The incidence of adverse events was also evaluated as an additional outcome.
Results
Eight studies were included with 1838 unique patients. Osimertinib plus chemotherapy demonstrated superior efficacy to Osimertinib alone in NSCLC tumours with CNS, liver, bone, or extrathoracic metastases, achieving a progression-free survival (PFS) of 25.5 months. Similar trends were observed in Chinese (PFS=27.4 months) and Japanese (PFS=14.5 months) populations. Secondary analyses from the FLAURA-2 trial indicated that patients with CNS metastases derived even more significant benefits than the general population (PFS=30.2 months). Common EGFR mutations, including exon 19 deletions and L858R, were assessed. The TAKUMI trial also evaluated the T790M resistance mutation, confirming consistent results. Patients with increased baseline tumor burden showed more significant benefits from the combination therapy (PFS=27.9 months) compared to Osimertinib alone. Similarly, data from recurrent NSCLC cases supported the combination’s efficacy (PFS=25.2 months). Safety analyses revealed a wide range of severe adverse events (grade 3 or higher), with rates between 20% and 83.8%, primarily due to pneumonia and interstitial lung disease.
Conclusions
Conclusion: Combining osimertinib and chemotherapy improves efficacy in patients with advanced EGFR-mutated NSCLC. The increased incidence of adverse effectswarrants careful patient selection. Further research is needed to optimize treatment strategies.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.