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Background: Patients with non-small cell lung cancer harbouring mesenchymal-epithelial transition exon 14 (METex14) skipping typically demonstrate poorer prognosis than overall non-small cell lung cancer. Until recently, no targeted treatments were available for patients with non-small cell lung cancer harbouring METex14 skipping in the UK, with limited treatments available., Objective: This study estimates the long-term survival and quality-adjusted life-year benefit of MET inhibitor tepotinib versus current standard of care from a UK perspective., Methods: A partitioned-survival model assessed the survival and quality-adjusted life-year benefits of tepotinib versus immunotherapy ± chemotherapy and chemotherapy for untreated and previously treated patients, respectively, using evidence from the single-arm VISION trial (NCT02864992). Two approaches were used to inform an indirect treatment comparison: (1) published clinical trials in overall non-small cell lung cancer and (2) real-world evidence in the METex14 skipping population. Results are presented as median and total quality-adjusted life-year gain and survival for progression-free survival and overall survival. Survival curves were validated against the external literature and uncertainty assessed using a probabilistic sensitivity analysis., Results: Using the indirect treatment comparison against the published literature, tepotinib is estimated to have a median progression-free survival gain versus pembrolizumab ± chemotherapy (11.0 and 9.2 months) in untreated patients, and docetaxel ± nintedanib (5.1 and 6.4 months) in previously treated patients. Across the populations, tepotinib is estimated to have a median survival gain of 15.4 and 9.2 months versus pembrolizumab ± chemotherapy in untreated patients and 12.8 and 5.1 months versus docetaxel ± nintedanib in previously treated patients. The total quality-adjusted life-year gain ranges between 0.56 and 1.17 across the untreated and previously treated populations. Results from the real-world evidence of indirect treatment comparisons are consistent with these findings., Conclusions: Despite the limitations of the evidence base, the numerous analyses conducted have consistently indicated positive outcomes for tepotinib versus the current standard of care., (© 2024. The Author(s).)

Introduction: Nivolumab demonstrated significant recurrence-free survival (RFS) gains versus ipilimumab in the CheckMate-238 trial, whereas the CA184-029 trial showed superior RFS gains for ipilimumab versus placebo. No head-to-head trial data were available to compare the efficacy of nivolumab to that of observation, so indirect treatment comparisons were required. Additionally, overall survival (OS) data were not available from CheckMate-238, and the clinical pathway for melanoma has changed significantly over the last decade. Four modelling options were developed using different methods and evidence sources to estimate OS and the impact of nivolumab on predicted life-years in the adjuvant setting; however, this article focuses on two primary methods., Methods: RFS for nivolumab and observation were informed by a patient-level data meta-regression. The first model was a partitioned survival model, where the parametric OS curve for observation was derived from CA184-029 and nivolumab OS was based on a surrogacy relationship between RFS and OS specific to adjuvant melanoma. The other option used a state-transition model to estimate post-recurrence survival using different data sources., Results: The modelling options estimated different OS for both nivolumab and observation but demonstrated at least a 32% increase in life-years gained for nivolumab versus observation., Conclusion: This analysis demonstrated the difficulties in modelling within the adjuvant setting. Each model produced different survival projections, showing the need to explore different techniques to address the extent of uncertainty. This also highlighted the importance of understanding the impact of RFS in the long term in a setting where the aim of treatment is to remain disease free.

Background: There is an unmet need for effective therapies for patients with advanced or metastatic urothelial cancer who cannot tolerate cisplatin-based chemotherapy. Cisplatin-ineligible patients experience a high frequency of adverse events from the most commonly used standard of care treatment, carboplatin plus gemcitabine, or alternative treatment with gemcitabine monotherapy. Pembrolizumab is a potent, highly selective humanised monoclonal antibody that releases checkpoint inhibition of the immune response system, and provides a new alternative for these patients., Objective: To assess the cost-effectiveness of pembrolizumab for first-line treatment of urothelial carcinoma ineligible for cisplatin-based therapy in patients with strongly PD-L1-positive tumours in Sweden., Design, Setting, and Participants: Parametric survival curves were fitted to overall survival, progression-free survival, and time on treatment data from KEYNOTE-052 to extrapolate clinical outcomes. A simulated treatment comparison and a network meta-analysis were conducted to estimate the comparative efficacy of pembrolizumab versus carboplatin plus gemcitabine and gemcitabine monotherapy. EQ-5D data from KEYNOTE-052 were used to estimate utility, while resource use and cost inputs were estimated using Swedish regional pricing lists and clinician opinion., Outcome Measurements and Statistical Analysis: The model reported costs, life years, and quality-adjusted life years (QALYs), and results were tested using deterministic and probabilistic sensitivity analysis., Results and Limitations: We estimated that pembrolizumab would improve survival by 2.11 and 2.16 years and increase QALYs by 1.71 and 1.75 compared to carboplatin plus gemcitabine and gemcitabine monotherapy, respectively. Pembrolizumab was associated with a cost increase of €90520 versus carboplatin plus gemcitabine and €95055 versus gemcitabine, with corresponding incremental cost-effectiveness ratios of €53055/QALY and €54415/QALY., Conclusions: At a willingness-to-pay threshold of €100000/QALY, pembrolizumab is a cost-effective treatment versus carboplatin plus gemcitabine and versus gemcitabine., Patient Summary: This is the first analysis to show that pembrolizumab is a cost-effective option for first-line treatment of cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma in Sweden., (Copyright © 2018 Merck Sharp & Dohme Corp and The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Studies into the effectiveness of interventions for upper limb soft tissue disorders have been hampered by a lack of consistently used diagnostic criteria, meaning that comparison of research results is a problem. To aid homogeneous recruitment into a study of de Quervain's disease, a de Quervain's screening tool (DQST) was developed. This could also be used to facilitate clinical diagnosis and management in practice., Aims: To provide evidence for the content and construct validity and test-retest and inter-rater reliability of the DQST., Method: The study was conducted in an acute care, outpatient hand unit in a district general hospital. Three convenience samples of: 59 people with de Quervain's disease; 18 with carpal tunnel syndrome (CTS) and 16 with osteoarthritis (OA) of the carpometacarpal (CMC) joint were recruited. The DQST diagnostic criteria were initially generated from a literature review. Content validity was then established by expert doctors with an interest in upper limb musculoskeletal disorders (n = 7) rating the relevance of the seven items included. The DQST was then tested in people either already diagnosed with, or reported as having some of the symptoms of, de Quervain's disease. Construct validity was tested with people with CTS or OA of the CMC joint., Results: The median DQST score was 5 (Interquartile range IQR = 4-6) out of a possible seven diagnostic criteria. Inter-rater reliability was excellent (Intra-class coefficient [ICC] = 0.85; 95% confidence interval [CI] = 0.75, 0.91). Test retest reliability was good (ICC = 0.64; 95% CI = 0.20, 0.87). Sensitivity (Se) and specificity (Sp) testing (Se = 1.00; Sp = 1.00) demonstrated that the DQST discriminated between people with de Quervain's disease, CTS or OA of the CMC joint., Conclusions: The DQST is a valid, reliable tool which could be of assistance in aiding correct diagnosis for recruitment to clinical trials and in clinical practice. Future research is recommended to further examine retest reliability with a larger sample size and to identify the commonest diagnostic criteria required for inclusion., ((c) 2008 John Wiley & Sons, Ltd.)