Raúl Díez

Objectives: To estimate the added value of dostarlimab compared to durvalumab and pembrolizumab as first-line treatment for adult patients with primary advanced or recurrent endometrial cancer (EC) in Spain using a Multi-Criteria Decision Analysis (MCDA) framework. Methods: Following the Evidence and Value: Impact on Decision Making (EVIDEM) framework and International Society for Pharmacoeconomics and Outcomes Research (ISPOR) recommendations, 25 Spanish experts (12 medical oncologists and 13 hospital pharmacists) weighted and scored 11 quantitative and 5 qualitative criteria based on an evidence matrix from a literature review. Results: Efficacy and safety were weighted as the most important criteria. Dostarlimab showed positive added value in both comparisons with scores of 0.58 versus durvalumab/durvalumab + olaparib and 0.50 versus pembrolizumab. Dostarlimab and pembrolizumab are the only therapies reimbursed in the Spanish public health system; therefore, their comparative assessment is of clinical and strategic relevance. While pembrolizumab may show longer progression-free survival (PFS) and response duration in specific subgroups, the evidence for dostarlimab—including a statistically significant improvement in overall survival (OS) in the overall population as a primary endpoint, more robust data, and favorable long-term quality-of-life outcomes—was considered by the expert panel to support a more favorable assessment. Conclusions: Within the MCDA framework, experts consider dostarlimab an option with a higher value contribution for adult patients with primary advanced or recurrent EC. Its clinical benefits, improved quality-of-life outcomes, and alignment with healthcare priorities promote treatment continuity and adherence in clinical practice. MCDA provided a transparent approach for multidimensional evaluation of these therapies.

Purpose: The addition of midostaurin to standard chemotherapy (cytarabine and daunorubicin) has shown significant improvements in the survival of patients with acute myeloid leukemia with the FLT3 mutation (FLT3-AML). The objective of this study was to determine whether this intervention would be cost-effective in Spain. Methods: A partitioned survival model with five health states was developed (diagnosis and induction, complete remission, no complete remission, transplantation and death). A lifetime time horizon and the Spanish National Health System perspective were adopted. During the first three years, permanence in the different health states was determined according to the results of the RATIFY study. In successive years, the death rates of the Spanish population adjusted by a factor to reflect long-term disease-related mortality were used. Utilities were obtained from the literature. Pharmacological costs (first and second line) and the costs of other health resources (hospitalizations, visits and tests) were included. The robustness of the model was evaluated by deterministic and probabilistic sensitivity analyses. Results: The addition of midostaurin resulted in 1.46 life years gained (LYG) and 1.23 quality-adjusted life years (QALY) gained and implied an additional cost of € 47,955, resulting in an incremental cost-effectiveness ratio (ICER) of € 32,854/LYG and an incremental cost-utility ratio of € 38,985/QALY. In the univariate sensitivity analysis, the threshold of € 50,000/QALY was not exceeded in any case; taking into consideration potential discounts of 20-40% in the PVL of midostaurin the ICER would be below € 30,000/QALY, a commonly accepted threshold in Spain. In the probabilistic analysis, when the threshold was € 50,000/QALY, midostaurin was cost-effective in 82.3% of simulations. Conclusion: According to our modeling, midostaurin, in combination with standard chemotherapy, could be an efficient alternative for the treatment of FLT3-AML in Spain.

Ethanol as an excipient is used to enhance the solubility of gemcitabine, but, sometimes, the dose of ethanol a patient may be given is much higher than the dose considered to be toxic. We aimed to assess ethanol-related symptoms and signs in patients receiving two formulations of gemcitabine, with and without ethanol. A randomized double blind cross-over study was conducted. All patients being treated with gemcitabine received two consecutive doses of the drug, one diluted from a concentrate for solution for infusion (CSI) containing ethanol and the other from a lyophilized powder, without ethanol, which was used as control group. After each administration, patients were surveyed in order to assess the appearance of any alcohol consumption symptoms (dizziness, difficulty speaking, unsteady walking, impaired balance, mood swings and slower reactions). Widmark formula and the amount of alcohol measured on the breath (breathalyzer) were used to estimate blood alcohol concentration. Twenty-four patients received both formulations and were included in the analysis. Mean administered ethanol dose when prepared from CSI was 15.81 ± 2.25 g (mean ± SD). When using CSI gemcitabine, estimated blood ethanol concentration was 0.033 g/dl according to Widmark formula and 0.02 g/dl according to breathalyzer results. Although overall incidence of symptoms was higher in the study group, the difference was not statistically significant (33% vs. 25%; p = 0.53). These findings prove there is no difference in the onset of ethanol related symptoms when using CSI instead of lyophilized powder on the reconstitution of gemcitabine.