IntroductionPalliative care (PC) has usually been offered at the end-of-life stage, although the WHO recommends providing PC as early as possible in the course of the disease. A recent study has shown that early PC (EPC) provides a more meaningful effect on quality of life and, surprisingly, on overall survival (OS) than standard treatment for patients with metastatic lung cancer. Whether EPC benefits also apply to patients with metastatic upper gastrointestinal (GI) cancers is unknown.Methods and analysisEPIC is a randomised phase III trial comparing EPC plus standard oncologic care versus standard oncologic care in patients with metastatic upper GI cancers. Its primary objective is to evaluate the efficacy of EPC in terms of OS. Its secondary objectives are to assess the effects of EPC on patient-reported outcomes (quality of life, depression and anxiety) and the effect of EPC on the number of patients receiving chemotherapy in their last 30 days of life. Assuming an exponential distribution of survival time, 381 deaths are required to ensure an 80% power for an absolute difference of 10% in 1 year OS rates (40% vs 50.3%, HR=0.75; log rank test two-sided alpha=5%), leading to a planned sample size of 480 patients enrolled over 3 years and a final analysis at 4 years. The main analysis will be performed on the intent-to-treat dataset.Ethics and disseminationThis study was approved by the ‘Comité de Protection des Personnes Nord-Ouest I’ (4 April 2016), complies with the Helsinki declaration and French laws and regulations and follows the International Conference on Harmonisation E6 (R1) Guideline for Good Clinical Practice. The trial results, even if they are inconclusive, will be presented at international oncology congresses and published in peer-reviewed journals.Trial registration numbersEudraCT: 2015-A01943-46; Pre-results. NCT02853474.
Three nucleoside reverse transcriptase inhibitor (NRTI) pairs are commonly used in the UK in people with HIV infection naïve to antiretroviral treatment. This analysis evaluated lifetime health outcomes, costs, and cost-effectiveness associated with once-daily tenofovir DF/emtricitabine (TDF/FTC), twice-daily zidovudine/lamivudine (ZDV/3TC), and once-daily abacavir/lamivudine (ABC/ 3TC).
MethodsResults of head-to-head clinical trials of TDF/FTC vs. ZDV/ 3TC (144-week results of Study 934) and ABC/3TC vs. ZDV/3TC (normalized 48-week results of Study CNA30024) were used to populate a Markov model that estimated lifetime costs and health outcomes for treatment-naïve individuals. Virologic response (< 400 copies/ mL) over time was estimated by fitting exponential curves to trial data; individuals with viral load levels above 400 copies/mL switched to second-line treatment. Immune response data were used to calculate transition probabilities between six health states based on CD4 cell-count ranges. Subsequent therapy lines were modeled using likely baskets of second-line, third-line, and non-suppressive therapy regimens. Utility values, mortality rates, drug costs and other direct medical costs were obtained from published sources. Adverse events observed in Studies 934 and CNA30024 were accounted for in modeled costs and outcomes. Base-case results were tested in one-way and probabilistic sensitivity analyses.
Summary of resultsIndividuals using TDF/FTC were predicted to remain on first-line therapy for an average of 5.9 years compared with 4.9 years and 4.8 years, respectively, for those using ABC/3TC and ZDV/3TC. Individuals using TDF/FTC were predicted to accrue total lifetime costs of £267,603 and experience 14.50 quality-adjusted life-years (QALYs), on average, compared with £269,487 and 14.38 QALYs and £266,785 and 14.20 QALYs for ABC/3TC and ZDV/3TC, respectively. The resulting cost-utility ratios were -£15,525 and £2,727 per QALY gained for TDF/FTC compared with ABC/3TC and ZDV/3TC, respectively.
ConclusionTDF/FTC was predicted to be both more effective and cost saving compared with ABC/3TC and to be cost-effective, using a threshold of £20,000 per QALY gained, compared with ZDV/3TC in treatment-naïve adults with HIV infection in the UK. In addition, TDF/FTC offers convenient, once-daily dosing. Results were driven by better efficacy and tolerability of TDF/FTC compared with the other NRTI pairs.
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