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Annals of Palliative Medicine Feb 2021Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been approved by the U.S. Food and Drug Administration in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been approved by the U.S. Food and Drug Administration in treating T790M mutationpositive advanced non-small cell lung cancer (NSCLC). A systematic review and meta-analysis was conducted to assess the efficacy and safety of osimertinib in treating advanced NSCLC patients with acquired T790M mutation.
METHODS
PubMed, EMBASE, Cochrane Library and Web of Science were searched to obtain the eligible studies following the "population, interventions, comparisons, outcomes, study design" (PICOS) criteria. The pooled analysis of objective response rate (ORR), disease controlled rate (DCR), progressionfree survival (PFS), overall survival (OS) and adverse events (AEs) were performed using STATA12.0 and RevMan5.0.
RESULTS
A total of 1,050 patients were included in the meta-analysis. The combined osimertinib ORR was 0.64 (95% CI, 0.60-0.69), the ORR of central nervous system (CNS) was 0.54 (95% CI, 0.37-0.71), DCR was 0.89 (95% CI, 0.86-0.92), PFS at six months (PFS-6m) rate was 0.69 (95% CI, 0.58-0.79), PFS at one year (PFS-1y) rate was 0.33 (95% CI, 0.20-0.46), OS at one year (OS-1y) rate was 0.69 (95% CI, 0.55-0.84). The pooled incidence rate of the AEs of grade ≥ III was 0.25 (95% CI, 0.09-0.40). The results from Begg's and Egger's tests presented no publication bias in the included studies.
CONCLUSIONS
Osimertinib demonstrated a superior therapeutic benefit with high efficacy and low toxicity for T790M-positive advanced NSCLC patients who were treated with early-generation EGFR-TKIs. Meanwhile, osimertinib showed promising for the treatment of advanced patients with CNS metastases.
Topics: Acrylamides; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors
PubMed: 33474947
DOI: 10.21037/apm-20-1357 -
Annals of Palliative Medicine Sep 2020Osimertinib, a third-generation tyrosine kinase inhibitor (TKI), is the only Food and Drug Administration-approved third-generation epidermal growth factor receptor... (Meta-Analysis)
Meta-Analysis
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.
Topics: Acrylamides; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; Central Nervous System; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors
PubMed: 32954743
DOI: 10.21037/apm-20-605