Targeted oncology
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Meta Analysis Comparative Study
Comparative Efficacy of CDK4/6 Inhibitors Plus Aromatase Inhibitors Versus Fulvestrant for the First-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer: A Network Meta-Analysis.
Several endocrine therapies are available for postmenopausal women with hormone receptor-positive (HR +) advanced breast cancer (ABC). Given the absence of direct comparisons between fulvestrant and cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with aromatase inhibitors (AIs), which are both used as standard first-line treatments for ABC, an indirect comparison using a network meta-analysis may be advantageous for decision making. ⋯ Within the limitations of this network meta-analysis, the comparison indicates that CDK4/6is plus AIs might represent a better option for HR+ ABC as a first-line endocrine treatment compared with fulvestrant.
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Observational Study
Toxicities with Immune Checkpoint Inhibitors: Emerging Priorities From Disproportionality Analysis of the FDA Adverse Event Reporting System.
Immune checkpoint inhibitors (ICIs), including antibodies targeting cytotoxic T-lymphocyte associated protein 4 (CTLA4) and programmed cell death 1 or its ligand (PD1/PDL1), elicit different immune-related adverse events (irAEs), but their global safety is incompletely characterized. ⋯ This parallel approach through contemporary post-marketing analysis and OoSRs confirmed that ICIs are associated with a multitude of irAEs, with different reporting patterns between anti-CTLA4 and anti-PD1/PDL1 medications. Close clinical monitoring is warranted to early diagnose and timely manage irAEs, especially respiratory, endocrine, and hepatic toxicities, which warrant further characterization; patient- and drug-related risk factors should be assessed through analytical pharmaco-epidemiological studies and prospective multicenter registries.
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Patients harboring concomitant epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) arrangements constitute a small subgroup of non-small-cell lung cancer (NSCLC) patients. The efficacy of EGFR tyrosine kinase inhibitors (TKIs) and the ALK-specific TKI crizotinib in these patients has not been well-established. ⋯ Both first-generation EGFR TKIs and the ALK TKI crizotinib were effective in these patients. Sequential treatment with EGFR TKIs and crizotinib should be considered as a management option.
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Acquired epidermal growth factor receptor (EGFR) T790M mutation is the primary resistance mechanism to first-generation EGFR tyrosine kinase inhibitors (TKIs) used in advanced, EGFR mutation-positive non-small-cell lung cancer (NSCLC). Available data, predominantly in Asian patients, suggest that this mutation is also the major cause of resistance to the irreversible ErbB family blocker, afatinib. For EGFR T790M-positive patients who progress on EGFR TKI therapy, osimertinib is an effective treatment option. However, data on osimertinib use after afatinib are, to date, scarce. ⋯ EGFR T790M mutation is a major mechanism of acquired resistance to afatinib. Osimertinib confers high response rates after afatinib failure in EGFR T790M-positive patients and its use in sequence potentially allows extended chemotherapy-free treatment.
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Multicenter Study
Efficacy of Osimertinib in EGFR-Mutated Non-Small Cell Lung Cancer with Leptomeningeal Metastases Pretreated with EGFR-Tyrosine Kinase Inhibitors.
The prognosis of patients with non-small cell lung cancer (NSCLC) who develop leptomeningeal metastasis (LM) is poor. ⋯ In this non-selected population, osimertinib had remarkable efficacy in NSCLC patients with LM irrespective of the presence of the EGFR-T790M-resistance mutation. Osimertinib efficacy was rapid in several patients, even some with poor performance status.