Non-small cell lung cancer with MET amplification: review of epidemiology, associated disease characteristics, testing procedures, burden, and treatments.

Introduction: Mesenchymal-epidermal transition factor gene amplification (METamp) is being investigated as a therapeutic target in advanced non-small cell lung cancer (NSCLC). We reviewed the epidemiology and disease characteristics associated with primary and secondary METamp, as well as the testing procedures used to identify METamp, in advanced NSCLC. Economic and humanistic burdens, and the practice patterns and treatments under investigation for METamp were also examined. Methods: Embase and Medline (via ProQuest), ClinicalTrials.gov, and Cochrane Controlled Register of Trials (2015-2022) were systematically searched. Conference abstracts were searched via Embase and conference proceedings websites (2020-2022). The review focused on evidence from the United States; global evidence was included for identified evidence gaps. Results: The median rate of primary METamp in NSCLC across the references was 4.8% (n=4 studies) and of secondary METamp (epidermal growth factor receptor [EGFR]-mutant NSCLC) was 15% (n=10). Next-generation sequencing (NGS; n=12) and/or fluorescence in situ hybridization (FISH; n=11) were most frequently used in real-world studies and FISH testing most frequently used in clinical trials (n=9/10). METamp definitions varied among clinical trials using ISH/FISH testing (MET to chromosome 7 centromere ratio of ≥1.8 to ≥3.0; or gene copy number [GCN] ≥5 to ≥10) and among trials using NGS (tissue testing: GCN ≥6; liquid biopsy: MET copy number ≥2.1 to >5). Limited to no data were identified on the economic and humanistic burdens, and real-world treatment of METamp NSCLC. Promising preliminary results from trials enrolling patients with EGFR-mutated, METamp advanced NSCLC progressing on an EGFR-tyrosine kinase inhibitor (TKI) were observed with MET-TKIs (i.e., tepotinib, savolitinib, and capmatinib) in combination with EGFR-TKIs (i.e., gefitinib and osimertinib). For metastatic NSCLC and high-level METamp, monotherapy with capmatinib, crizotinib, and tepotinib are recommended in the 2022 published NSCLC NCCN Guidelines. Conclusion: Primary METamp occurs in approximately 5% of NSCLC cases, and secondary METamp in approximately 15% of cases previously treated with an EGFR inhibitor. Variability in testing methods (including ISH/FISH and NGS) and definitions were observed. Several treatments are promising in treating METamp NSCLC. Additional studies evaluating the clinical, economic, and humanistic burdens are needed.

Nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex - disease burden, unmet needs, and advances in treatment developments.

INTRODUCTION: Nontuberculous mycobacterial (NTM) lung disease (LD) is the most common clinical manifestation of NTM infection and is a growing health concern. Up to 85% of NTM-LD cases are caused by Mycobacterium avium complex (MAC). Increased awareness of NTM-LD caused by MAC is needed as patients with this disease experience substantial burden and unmet treatment needs. AREAS COVERED: This review provides clinicians and regulatory and healthcare decision makers an overview of the clinical, economic, and humanistic burden of NTM-LD and the unmet treatment needs faced by patients and clinicians. The review focuses on NTM-LD caused by MAC. A summary of the 2020 NTM guidelines specifically for MAC-LD and an overview of novel treatment options, including amikacin liposome inhalation suspension (ALIS) as the first approved therapy for refractory MAC-LD, and investigational drugs in testing phase are provided. EXPERT OPINION: Key advancements in NTM-LD management include recent updates to clinical practice guidelines, approval of ALIS for the treatment of refractory MAC-LD, and ongoing clinical trials of investigational treatments. Yet opportunities still exist to improve patient outcomes, including development of better screening tools, such as reliable and responsive biomarkers to help identify high-risk patients, and addressing unmet treatment needs.

Real-World Outcomes of Ivacaftor Treatment in People with Cystic Fibrosis: A Systematic Review.

Cystic fibrosis (CF) is a rare, progressive, multi-organ genetic disease. Ivacaftor, a small-molecule CF transmembrane conductance regulator modulator, was the first medication to treat the underlying cause of CF. Since its approval, real-world clinical experience on the use of ivacaftor has been documented in large registries and smaller studies. Here, we systematically review data from real-world observational studies of ivacaftor treatment in people with CF (pwCF). Searches of MEDLINE and Embase identified 368 publications reporting real-world studies that enrolled six or more pwCF treated with ivacaftor published between January 2012 and September 2019. Overall, 75 publications providing data from 57 unique studies met inclusion criteria and were reviewed. Studies reporting within-group change for pwCF treated with ivacaftor consistently showed improvements in lung function, nutritional parameters, and patient-reported respiratory and sino-nasal symptoms. Benefits were evident as early as 1 month following ivacaftor initiation and were sustained over long-term follow-up. Decreases in pulmonary exacerbations, Pseudomonas aeruginosa prevalence, and healthcare resource utilization also were reported for up to 66 months following ivacaftor initiation. In studies comparing ivacaftor treatment to modulator untreated comparator groups, clinical benefits similarly were reported as were decreases in mortality, organ-transplantation, and CF-related complications. The safety profile of ivacaftor observed in these real-world studies was consistent with the well-established safety profile based on clinical trial data. Our systematic review of real-world studies shows ivacaftor treatment in pwCF results in highly consistent and sustained clinical benefit in both pulmonary and non-pulmonary outcomes across various geographies, study designs, patient characteristics, and follow-up durations, confirming and expanding upon evidence from clinical trials.

Economic analysis of empiric versus diagnostic-driven strategies for immunocompromised patients with suspected fungal infections in the People's Republic of China.

Invasive fungal infections (IFIs) require rapid diagnosis and treatment. A decision-analytic model was used to estimate total costs and survival associated with a diagnostic-driven (DD) or an empiric treatment approach in neutropenic patients with hematological malignancies receiving chemotherapy or autologous/allogeneic stem cell transplants in Shanghai, Beijing, Chengdu, and Guangzhou, the People's Republic of China. Treatment initiation for the empiric approach occurred after clinical suspicion of an IFI; treatment initiation for the DD approach occurred after clinical suspicion and a positive IFI diagnostic test result. Model inputs were obtained from the literature; treatment patterns and resource use were based on clinical opinion. Total costs were lower for the DD versus the empiric approach in Shanghai (¥3,232 vs ¥4,331), Beijing (¥3,894 vs ¥4,864), Chengdu, (¥4,632 vs ¥5,795), and Guangzhou (¥8,489 vs ¥9,795). Antifungal administration was lower using the DD (5.7%) than empiric (9.8%) approach, with similar survival rates. Results from one-way and probabilistic sensitivity analyses were most sensitive to changes in diagnostic test sensitivity and IFI incidence; the DD approach dominated the empiric approach in 88% of scenarios. These results suggest that a DD compared to an empiric treatment approach in the People's Republic of China may be cost saving, with similar overall survival in immunocompromised patients with suspected IFIs.

Methicillin-resistant Staphylococcus aureus nosocomial pneumonia: role of linezolid in the People's Republic of China.

The burden of methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia in the People's Republic of China is high, with methicillin-resistance rates greater than 80% reported for patients with S. aureus pneumonia treated in intensive care units. Historically, vancomycin was the treatment of choice for patients with hospital-acquired MRSA infections. Recent evidence suggests that the minimum inhibitory concentration for vancomycin is increasing. Additionally, patients treated with vancomycin require monitoring of vancomycin trough concentrations and can develop nephrotoxicity. Linezolid is a treatment option for patients with hospital-acquired MRSA infections that can be administered either intravenously or orally. Analysis of data from a worldwide linezolid surveillance program initiated in the year 2004 shows no evidence of increasing linezolid minimum inhibitory concentrations. The clinical efficacy of linezolid for patients with gram-positive, including MRSA, nosocomial pneumonia, was evaluated in numerous studies. In general, results from these studies show higher or similar clinical success with no mortality difference for linezolid compared to vancomycin treated patients. Results from a Phase IV study enrolling patients with MRSA-confirmed nosocomial pneumonia suggest higher clinical cure rates for linezolid compared to vancomycin treated patients. Although acquisition costs are higher for linezolid compared to vancomycin therapy, evidence suggests similar overall medical costs. Cost-analysis results from a Chinese perspective show that linezolid dominated vancomycin therapy for MRSA nosocomial pneumonia in ∼35% of bootstrap simulations whereas vancomycin dominated linezolid in less than 2% of bootstrap simulations. In summary, results from both clinical and economic studies, including studies conducted from a Chinese perspective, support the use of linezolid for the treatment of patients with MRSA nosocomial pneumonia.

Economic evaluation of urgent-start peritoneal dialysis versus urgent-start hemodialysis in the United States.

Patients presenting late in the course of kidney disease who require urgent initiation of dialysis have traditionally received temporary vascular catheters followed by hemodialysis. Recent changes in Medicare payment policy for dialysis in the USA incentivized the use of peritoneal dialysis (PD). Consequently, the use of more expeditious PD for late-presenting patients (urgent-start PD) has received new attention. Urgent-start PD has been shown to be safe and effective, and offers a mechanism for increasing PD utilization. However, there has been no assessment of the dialysis-related costs over the first 90 days of care. The objective of this study was to characterize the costs associated with urgent-start PD, urgent-start hemodialysis (HD), or a dual approach (urgent-start HD followed by urgent-start PD) over the first 90 days of treatment from a provider perspective. A survey of practitioners from 5 clinics known to use urgent-start PD was conducted to provide inputs for a cost model representing typical patients. Model inputs were obtained from the survey, literature review, and available cost data. Sensitivity analyses were also conducted. The estimated per patient cost over the first 90 days for urgent-start PD was $16,398. Dialysis access represented 15% of total costs, dialysis services 48%, and initial hospitalization 37%. For urgent-start HD, total per patient costs were $19,352, and dialysis access accounted for 27%, dialysis services 42%, and initial hospitalization 31%. The estimated cost for dual patients was $19,400. Urgent-start PD may offer a cost saving approach for the initiation of dialysis in eligible patients requiring an urgent-start to dialysis.