Pembrolizumab monotherapy survival benefits in metastatic non-small-cell lung cancer: a systematic review of real-world data.

The efficacy of pembrolizumab in the treatment-naïve non-small-cell lung cancer (NSCLC) patients was proved in the KEYNOTE-024 randomized trial. The aim of this systematic literature review was to identify and summarize the real world evidence (RWE) of overall survival (OS) in previously untreated patients with NSCLC receiving pembrolizumab monotherapy. A systematic search was conducted in PubMed (MEDLINE®) and EMBASE databases. Analyses were focused on survival data (median OS and survival rates at specific time points). To explore the population comparable with the KEYNOTE-024 study, we focused on studies enrolling at least 50% of patients at stage IV of cancer and ECOG performance status 0-2. A total of 41 RWE studies covering over 7600 advanced NSCLC patients naïve to systemic treatment were identified. Overall, survival outcomes reported in those studies vary considerably (median OS range: 3.0-34.6 months). Most RWE studies reported median OS shorter to that reported in KEYNOTE-024 (26.3 months), but about half of reported OS medians were in range of 95% confidence interval for OS as reported in KEYNOTE-024 trial (18.3-40.4 months). Patients with similar characteristics of stage and performance status to those of KEYNOTE-024 trial benefited the same with pembrolizumab monotherapy as their survival outcomes (18.9-22.8 months) were consistent with those reported in the clinical trial. RWE data showed substantially worse outcomes in patients with ECOG-PS 2+ compared to ECOG-PS 0-1 patients.

Immune checkpoint inhibitors combined with tyrosine kinase inhibitors or immunotherapy for treatment-naïve metastatic clear-cell renal cell carcinoma-A network meta-analysis. Focus on cabozantinib combined with nivolumab.

Introduction: The combination of immunotherapy and targeted therapy is currently marking a new era in the treatment of renal cancer. The latest clinical guidelines recommend the use of drug combinations for the first-line treatment of advanced renal cancer. The aim of this review is to compare the efficacy of combined cabozantinib + nivolumab therapy with other immune checkpoint inhibitors combined with tyrosine kinase inhibitors or monoclonal antibodies blocking the CTLA-4 (cytotoxic T cell antigen 4) in the first-line treatment of metastatic clear-cell renal cell carcinoma (RCC). Methodology: A systematic literature search was carried out in the PubMed and EMBASE databases. Randomized controlled trials (RCTs) on therapies recommended by the latest EAU and ESMO guidelines for treatment-naïve metastatic RCC (i.e., lenvatinib + pembrolizumab, axitinib + pembrolizumab and nivolumab + ipilimumab) were searched. A network meta-analysis (NMA) was performed for data synthesis. The methodology of included RCTs was assessed using the Cochrane RoB two tool. The data were analyzed in the overall population as well as in risk subgroups defined according to the International Metastatic Database Consortium (IMDC) i.e., patients with a favorable and intermediate or poor prognoses. The most recent cut-off dates from included studies were analyzed. Results: Four RCTs (CheckMate 9 ER, KEYNOTE-426, CLEAR and CheckMate 214) were included in the review. No studies directly comparing cabozantinib + nivolumab with any of the drug combinations included in this review were available. NMA showed that cabozantinib + nivolumab was superior compared to axitinib + pembrolizumab and nivolumab + ipilimumab in all analyzed comparisons (overall population and IMDC risk subgroups), both in terms of overall survival and progression-free survival (PFS). The advantage of cabozantinib + nivolumab was statistically significant only for PFS when compared to nivolumab + ipilimumab in the overall population. The results for the comparison of cabozantinib + nivolumab with lenvatinib + pembrolizumab showed numerical superiority of lenvatinib + pembrolizumab combination in terms of overall survival, but none of the results were statistically significant. The advantage of lenvatinib + pembrolizumab over cabozantinib + nivolumab in terms of PFS was statistically significant in the overall and favorable prognosis population. Conclusion: Inclusion of the most recent cut-off data from CheckMate 9 ER did not affect the role of the cabozantinib + nivolumab combination for treatment-naïve metastatic RCC. Cabozantinib + nivolumab is an effective therapeutic option for the first-line treatment of advanced renal cancer that is recommended both in the latest European and American guidelines for all IMDC risk groups.

Health related quality of life in patients with diabetic foot ulceration - translation and Polish adaptation of Diabetic Foot Ulcer Scale short form.

OBJECTIVES: Diabetic foot ulcer (DFU) is a common complication of diabetes and not only an important factor of mortality among patients with diabetes but also decreases the quality of life. The short form of Diabetic Foot Ulcer Scale (DFS-SF) provides comprehensive measurement of the impact of diabetic foot ulcers on patients' health related quality of life (HRQoL). The purpose of this study was to translate DFS-SF into Polish and evaluate its psychometric performance in patients with diabetic foot ulcers. METHODS: The DFS-SF translation process was performed in line with Principles of Good Practice for the Translation and Cultural Adaptation Process for patient reported outcome measures (PROMs) developed by ISPOR TCA group. Assessment of the reliability and validity of Polish DFS-SF was performed in native Polish patients with current DFU. RESULTS: The DFS-SF validation study involved 212 patients diagnosed with DFU, with 4.4 years of DFU duration on average. The average ulcer size was 5.5 sq. cm, and generally only one limb was affected. Men (72%) and type 2 diabetes patients (86%) prevailed, with 17.8 years representing the mean time since diagnosis. The mean population age was 62.5 years. The internal consistency of all scales of the Polish DFS-SF was high (Cronbach's alpha ranged from 0.82 to 0.93). Item convergent and discriminant validity was satisfactory (median corrected item-scale correlation ranged from 0.61 to 0.81). The Polish DFS-SF demonstrated good construct validity when correlated with the SF-36v2 and showed better psychometric performance than SF-36v2. CONCLUSIONS: The newly translated Polish DFS-SF may be used to assess the impact of DFU on HRQoL in Polish patients.

Direct healthcare costs and cost-effectiveness of acute coronary syndrome secondary prevention with ticagrelor compared to clopidogrel: economic evaluation from the public payer's perspective in Poland based on the PLATO trial results.

BACKGROUND: Ticagrelor is the first reversibly binding oral P2Y12 receptor antagonist designed to reduce clinical thrombotic events in patients with acute coronary syndrome (ACS). Compared to clopidogrel, ticagrelor has been proven to significantly reduce the rate of death from vascular causes, myocardial infarction (MI), or stroke without an increase in the rate of overall major bleeding in patients who have an ACS with or without ST-segment elevation (STEMI and NSTEMI) or unstable angina (UA). AIM: To evaluate the cost-effectiveness and healthcare costs associated with secondary prevention of ACS using ticagrelor or clopidogrel in patients after STEMI, NSTEMI and UA. METHODS: An economic model based on results from the PLATO trial was used to evaluate the cost-effectiveness of one-year therapy with ticagrelor or clopidogrel. The structure of the model consisted of two parts, i.e. the decision tree with one-year PLATO results and the Markov model with lifelong estimations, which exceeded PLATO follow-up data. The model was adjusted to Polish settings with country-specific data on death rates in the general population and direct medical costs calculated from the public payer's perspective. Costs were derived from the National Health Fund (NHF) and the Ministry of Health and presented in PLN 2013 values. Annual mean costs of second and subsequent years after stroke or MI were obtained from the literature. Uncertainty of assumed parameters was tested in scenarios and probabilistic sensitivity analyses. The adopted model allowed the estimation of an incremental cost-effectiveness ratio for life years gained (LYG) and an incremental cost-utility ratio for quality adjusted life years (QALY). RESULTS: Total direct medical costs to the public payer at a one year horizon were 2,905 PLN higher with ticagrelor than with clopidogrel. However, mean healthcare costs at a one year horizon (excluding drug costs and concomitant drugs) were 690 PLN higher for patients treated with clopidogrel. In a lifetime horizon, results indicated that ticagrelor was the more cost-effective option compared to generic clopidogrel, with an incremental cost per LYG estimated at 21,566 PLN and an incremental costper QALY estimated at 24,965 PLN. CONCLUSIONS: In a lifetime horizon, which should be used when comparing technologies with different impacts on mortality, cost-effectiveness evaluation resulted in more favourable economic outcomes for ticagrelor than for generic clopidogrel, with the cost per QALY well below the recommended willingness to pay threshold in Poland (24,965 PLN vs. 111,381 PLN).

The indirect costs of cancer-related absenteeism in the workplace in Poland.

OBJECTIVES: The aim of this study was to evaluate cancer-related absenteeism costs in Poland. METHODS: Data on sickness absences and disability were retrieved from the Department of Statistics of the Social Insurance Institution. The cost of lost productivity owing to premature death was estimated from data retrieved from the Polish National Cancer Registry. Absenteeism costs were estimated on the basis of the measure of gross value added per employee. RESULTS: The costs of lost productivity owing to sick leave, disability, and premature death were estimated to be 1.572 billion EUR, 0.504 billion EUR, and 0.535 billion EUR, respectively, in 2009. CONCLUSIONS: The indirect costs of lost productivity owing to cancer-related sick leave, disability, and premature death have a substantial effect on the Polish economy. In 2009, they accounted for more than 0.8% of GDP.

[Cost of lost productivity in pharmacoeconomics analysis. Part I. A systematic review of the literature]. / Koszty utraconej produktywnosci w analizach farmakoekonomicznych. Czesc i. Przeglad systematyczny pismiennictwa.

The inclusion of indirect costs of illness in economic studies is still a subject of considerable debate. The aim of the systematic literature review was to present the Polish economic practice concerning indirect costs evaluation of healthcare interventions. MEDLINE, EMBASE, Cochrane Library and Polish Medical Bibliography (PBL) were searched. Cut-off dates were set to February and March 2009. The main specific keywords were 'indirect costs' or 'costs and cost analysis'. Nineteen studies fulfilled the inclusion criteria for this review, of a total of 2300 references. Seventeen out of 19 studies were cost of illness studies, 2 were economic analyses. Methods of indirect costs evaluation were all based on human capital approach. The work absenteeism unit time measure used to value productivity loss were average salary (9/19), Gross Domestic Product (GDP) per capita (7/19), Gross National Product per capita (1/19), GDP per active worker (1/19), sold production of industry per active worker (1/19). Mean indirect costs were ca. 58% of total costs (range: 16%-98%). In 5 studies transfer payments were added to productivity loss category. Indirect cost is rarely included in the economic analyses in Poland. Various methods of indirect costs calculation limit comparison between studies and support the need for development of robust and widely accepted methodology.

[Indirect costs in health technology assessment]. / Koszty posrednie w ocenie technologii medycznych.

In the health technology assessment it is crucial to define the perspective of the analysis. When the societal perspective is chosen it is necessary to include all the costs incurred by the society, also the costs of lost productivity resulting from absence of sick employees from work or their reduced efficiency at work. The aim of this article is to present the notion of indirect costs, their importance in health technology assessment and the methods of calculation. The economic literature has been reviewed for the state of knowledge on indirect costs. Three methods of calculation are described: human capital method, friction cost method or health state valuation. Indirect costs in Western European countries can amount to more than half of total costs attributed to the illness and its treatment. In the literature there is no consensus regarding the proper method of indirect costs calculation. It is necessary to conduct further theoretical and empirical research in the area of indirect costs and enhance discussion among Polish pharmacoeconomists.