Ανάλυση κόστους - αποτελεσματικότητας του Pertuzumab έναντι εικονικού φαρμάκου σε HER2 θετικό μεταστατικό καρκίνο του μαστού

Abstract

Breast cancer is one of the most common cancers worldwide. Based on the findings of the interim analysis of the clinical trial CLEOPATRA (NCT00567190) conducted in 2015, Pertuzumab resulted in an unprecedented absolute increase in Overall Survival by 15.7 months. After a median follow-up of 50 months, the median Overall Survival was 56.5 months for the Pertuzumab group and 40.8 months for the placebo group respectively. At the time, a 32% reduction in mortality was recorded, (hazard ratio 0.68, p<0.001). Over the whole duration of the study (end-of-study analysis), the median Overall Survival of Pertuzumab was 57.1 months while for the control group was 40.8 months respectively. In other words, there was an absolute difference of 16.3 months in favor of the intervention group. Also important is the fact that the overall safety profile of the triplet was consistent with the safety profile of Pertuzumab. It was not associated with a higher incidence of symptomatic left ventricular dysfunction (LVD) or reductions in the left ventricular ejection fraction (LVEF) compared to placebo and the simple combination of Trastuzumab and Docetaxel. Pertuzumab (Perjeta®) is a recombinant humanized monoclonal antibody that, as a key function, inhibits intracellular growth factor (HER2) signaling pathways and can lead to inhibition of cell proliferation and apoptosis, respectively.(www.ema.europa.eu, SPC). Pertuzumab was approved by the US FDA (Food and Drug Administration) on June 8, 2012, while in Greece the first approval was given on March 4, 2013. The cost-effectivenessof the combination of Pertuzumab, Trastuzumab and Docetaxel compared with the simple combination of Trastuzumab and Docetaxel in HER-2 positive metastatic breast cancer has not been evaluated in Greece. The purpose of this analysis is to evaluate the cost-effectiveness of Pertuzumab compared to the simple combination as a first-line treatment for patients with HER-2 positive metastatic breast cancer, in Greece. The viewpoint of the analysis is that of the Greek National Health System. The analysis uses a Markov model. The model was comprised of three health states: Progression Free (PFS), Progressed Disease (PD) and death. The population of interest was adults 54 years old at the start of the model with HER-2 positive metastatic breast cancer. The data used to populate the model were drawn from international and Greek published sources. The model follows a hypothetical group of patients from the beginning of treatment till death over monthly cycles. Data and probabilities for OS and PFS were derived from the clinical trial CLEOPATRA, and were extrapolated to a period of 120 months thus covering the life expectancy of these patients (lifetime analysis). Clinical effectiveness was assessed in terms of life expectancy and quality adjusted life expectance and the corresponding cost was estimated by combining the volume of resources used with their unit costs based on NHS current prices. The cost and effectiveness were calculated for each health state, per cycle and per patient. In addition sensitivity analysis was performed due to the uncertainties introduced by model parameters. The triplet combination of pertuzumab/trastuzumab/docetaxel compared to placebo/trastuzumab/docetaxel as first line treatment in adult patients with HER2 positive metastatic breast cancer was more costly per patient, while at the same time improved the life expectancy (LYs) and the quality of life (QALYs). The ICER was estimated at €197,844.95/QALY gained and at €123,653.09/LY gained for the life expectancy of those patients. The sensitivity analysis showed that the results are sensitive to drug unit cost and do not appear to be sensitive to the discount rate. According to the results of this study, Pertuzumab compared to placebo as a treatment for HER2 positive metastatic breast cancer, is considered a non cost-effective treatment option for the National Health System of Greece.