Objective. To determine the pharmacoeconomical feasibility of using a combination of atezolizumab + nab-paclitaxel in the 1st line of therapy for locally advanced or metastatic triple negative breast cancer (TNBC) in adult PDL1 positive patients in the Russian healthcare system. Materials and methods. A decision analysis model was used followed by Markov modelling for the economic evaluation of the drugs in the treatment of metastatic TNBC. We used the «cost-effectiveness» analysis and the «impact on the budget» (BIA) analysis. Two therapeutic approaches were evaluated: the use of combined therapy with atezolizumab + nab-paclitaxel and monotherapy with nab-paclitaxel. The analysis included direct costs. Additionally, the obtained pharmacoeconomical indicators of the use of a combination of atezolizumab and nab-paclitaxel and other drugs for the treatment of locally advanced and metastatic breast cancer were compared. Results. The use of the estimated therapeutic approaches in the treatment of metastatic TNBC was characterized by the following costs: with a modelling horizon of 1 year, the cost of using atezolizumab in combination with nab-paclitaxel was 5,076,321 rubles per patient. The costs for the use of single agent nab-paclitaxel with was 60 % less than: — 2 020 038,78 RUB. At the same time, the effectiveness of therapy with a combination of atezolizumab and nab-paclitaxel clinically significantly exceeded that of nab-paclitaxel monotherapy: a 38 % reduction in the risk of death or progression, a 10-fold increase in the frequency of complete response to therapy (10 vs 1 %), and a 7-month increase in the median overall survival (25 vs 18 months). The economic evaluation of the combination of atezolizumab with nab-paclitaxel was carried out with the calculation of the incremental cost-effectiveness ratios (ICER) — the calculation of the additional cost for each additional year of life in comparison with standard therapy. Due to the fact that currently in Russia for patients with metastatic TNBC no similar performance modes of therapy ICER for the combination atezolizumab + nab-paclitaxel compared with the ICER for palbociclib in combination with fulvestrant (drugs, showed improved overall survival in clinical research and included in clinical guidelines for the treatment of diseases of the same class ICD-10 in locally advanced and metastatic breast cancer). The ICER for overall survival at the end of the first year of follow-up for atezolizumab + nab-paclitaxel and palbociclib + fulvestrant was 30.5 million rubles and 47.4 million rubles, respectively. For the combination of atezolizumab + nab-paclitaxel, ICER is lower than the similar ICER for the palbociclib + fulvestrant mode by 36 %. Analysis of trends in the weighted average cost of systemic pathogenetic treatment of breast cancer (breast cancer) shows the following: increased use of the combination of atezolizumab + nab-paclitaxel for the treatment of patients with metastatic TNBC doesn’t lead to a considerable growth in the cost of therapy in patients with breast cancer — providing therapy to 1400 patients that includes the entire target population of patients with TNBC and expression of PD-L1 in Russia changes in the costs of chemotherapy and immunotherapy of breast cancer will remain within 2.6 %. Conclusion. Pharmacoeconomic indicators of the use of atezolizumab in combination with nab-paclitaxel are more cost-effective in comparison with other expensive schemes for the treatment of breast cancer, and tumors of other localities that are actively used in current practice, which suggests the acceptability and feasibility of introducing and expanding the use of this therapeutic option in the target population.
Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer