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Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Osimertinib for EGFR-mutant lung cancer with central nervous system metastases: a meta-analysis and systematic review
Na Wang1, Yaozhong Zhang2, Yuan Mi2
1Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Background:
Osimertinib, a third-generation tyrosine kinase inhibitor (TKI), is the only Food and Drug Administration-approved third-generation epidermal growth factor receptor (EGFR)TKI. Osimertinib is a cancer medicine that interferes with the growth and spread of cancer cells in the body. Osimertinib is used to treat a certain type of non-small cell lung cancer. We review some of the main challenges in targeting EGFR, including lack of central nervous system penetration with most tyrosine kinase inhibitors, activity of osimertinib penetrating blood-brain barrier and the efficacy of osimertinib.
Methods:
Guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, we conducted a systematic literature search in the databases PubMed, EMBASE, ISI Web of Science database on January 30, 2020, searching for studies investigating the osimertinib efficacy on patients with CNS metastases in EGFR-mutant non-small cell lung cancer (NSCLC). And Newcastle-Ottawa Scale (NOS) was used to assess the certainty in the evidence.
Results:
The pooled results showed that the overall response rate (ORR) and disease control rate (DCR) were 70% and 92%, respectively, in patients with T790M mutations. The efficacy of osimertinib was confirmed by the median progression free survival (PFS). In untreated advanced EGFR-mutated NSCLC with CNS metastases patients, the pooled ORR and DCR of osimertinib were 71% and 93%, respectively. And the combined median PFS, achieved by osimertinib, was 12.21 months. Above data proved that osimertinib has well activity in disease control, especially in first line.
Conclusions:
This meta-analysis confirmed that in treatment-naive advanced NSCLC CNS metastases harboring EGFR-TKI-sensitizing mutations, Osimertinib showed impressive antitumor activity.
Insights
Osimertinib effectively treats non-small cell lung cancer (NSCLC) with brain metastases. This third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) demonstrates significant antitumor activity and improves progression-free survival in patients.
Area of Science:
- Oncology
- Pharmacology
Background:
- Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved for specific non-small cell lung cancer (NSCLC) treatments.
- A key challenge in EGFR-TKI therapy is achieving sufficient central nervous system (CNS) penetration, which Osimertinib addresses.
- This review focuses on Osimertinib's efficacy, particularly its ability to penetrate the blood-brain barrier.
Purpose of the Study:
- To systematically evaluate the efficacy of Osimertinib in patients with EGFR-mutant non-small cell lung cancer (NSCLC) and central nervous system (CNS) metastases.
- To assess Osimertinib's antitumor activity and impact on progression-free survival (PFS) in this patient population.
Main Methods:
- A systematic literature search was conducted across PubMed, EMBASE, and ISI Web of Science databases up to January 30, 2020.
- Studies investigating Osimertinib efficacy in EGFR-mutant NSCLC patients with CNS metastases were included, adhering to PRISMA guidelines.
- The Newcastle-Ottawa Scale (NOS) was utilized to evaluate the certainty of the evidence.
Main Results:
- Pooled analysis revealed an overall response rate (ORR) of 70% and disease control rate (DCR) of 92% in patients with T790M mutations.
- In treatment-naive advanced EGFR-mutated NSCLC patients with CNS metastases, Osimertinib achieved an ORR of 71% and DCR of 93%.
- The median progression-free survival (PFS) with Osimertinib in this cohort was 12.21 months, demonstrating significant disease control.
Conclusions:
- Osimertinib exhibits impressive antitumor activity in treatment-naive advanced NSCLC patients with CNS metastases harboring EGFR-TKI-sensitizing mutations.
- The drug's efficacy in controlling disease, especially as a first-line treatment, is well-supported by the findings.
- Osimertinib's ability to penetrate the CNS is crucial for its effectiveness in managing brain metastases.
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