Cost-effectiveness of nivolumab in the treatment of head and neck cancer.

BACKGROUND: Until recently, no second-line treatment for recurrent and/or metastatic head and neck squamous cell cancer (r/mHNSCC) was able to improve overall survival (OS). Nivolumab has become a promising treatment for r/mHNSCC. The CheckMate-141 trial showed that nivolumab improves OS compared to investigator's choice (IC) (cetuximab, methotrexate, docetaxel). Treatment with immune checkpoint inhibitors is however expensive. The aim of this analysis was to assess the cost-effectiveness of nivolumab as second-line treatment for r/mHNSCC in Switzerland. METHODS: Based on the CheckMate-141 trial, we constructed a Markov model comparing nivolumab to IC, including follow-up data up to 24 months. We assessed costs for treatments from the perspective of the Swiss health system with a 60 months' time horizon. PD-L1 and p16 testing were considered in scenarios. Incremental cost-effectiveness ratios (ICER) were compared to an informal willingness-to-pay of CHF (Swiss Francs) 100,000 per QALY gained. RESULTS: For the base case we estimated an incremental effectiveness of 0.35 QALYs and incremental costs of CHF 35,562 with nivolumab, resulting in an ICER of CHF 102,957 per QALY gained. Most influential drivers for the ICER were the price of nivolumab and the progressive disease state utility weights. In 45.5% of probabilistic sensitivity analysis simulations nivolumab was estimated below 100,000 CHF/QALY. Reducing the price of nivolumab according to a consented payback by 4.75%, resulted in an ICER of CHF 98,325/QALY gained. CONCLUSIONS: At current prices nivolumab has an ICER of around CHF 100,000 per QALY gained in the second line treatment of r/mHNSCC patients in Switzerland.

Days spent in acute care hospitals at the end of life of cancer patients in four Swiss cantons: a retrospective database study (SAKK 89/09).

Number of days spent in acute hospitals (DAH) at the end of life is regarded as an important care quality indicator for cancer patients. We analysed DAH during 90 days prior to death in patients from four Swiss cantons. Claims data from an insurance provider with about 20% market share and patient record review identified 2086 patients as dying of cancer. We calculated total DAH per patient. Multivariable generalised linear modelling served to evaluate potential explanatory variables. Mean DAH was 26 days. In the multivariable model, using complementary and alternative medicine (DAH = 33.9; +8.8 days compared to non-users) and canton of residence (for patient receiving anti-cancer therapy, Zürich DAH = 22.8 versus Basel DAH = 31.4; for other patients, Valais DAH = 22.7 versus Ticino DAH = 33.7) had the strongest influence. Age at death and days spent in other institutions were additional significant predictors. DAH during the last 90 days of life of cancer patients from four Swiss cantons is high compared to most other countries. Several factors influence DAH. Resulting differences are likely to have financial impact, as DAH is a major cost driver for end-of-life care. Whether they are supply- or demand-driven and whether patients would prefer fewer days in hospital remains to be established.

Palbociclib as a first-line treatment in oestrogen receptor-positive, HER2-negative, advanced breast cancer not cost-effective with current pricing: a health economic analysis of the Swiss Group for Clinical Cancer Research (SAKK).

Endocrine therapy continues to be the optimal systemic treatment for metastatic ER(+)HER2(-) breast cancer. The CDK4/6 inhibitor palbociclib combined with letrozole has recently been shown to significantly improve progression-free survival. Here we examined the cost-effectiveness of this regimen for the Swiss healthcare system. A Markov cohort simulation based on the PALOMA-1 trial (Finn et al. in Lancet Oncol 16:25-35, 2015) was used as the clinical course. Input parameters were based on summary trial data. Costs were assessed from the Swiss healthcare system perspective. Adding palbociclib to letrozole (PALLET) compared to letrozole monotherapy was estimated to cost an additional CHF342,440 and gain 1.14 quality-adjusted life years, resulting in an incremental cost-effectiveness ratio (ICER) of CHF301,227/QALY gained. In univariate sensitivity analyses, no tested variation in key parameters resulted in an ICER below a willingness-to-pay threshold of CHF100,000/QALY. PALLET had a 0 % probability of being cost-effective in probabilistic sensitivity analyses. Lowering PALLET's price by 75 % resulted in an ICER of CHF73,995/QALY and a 73 % probability of being cost-effective. At current prices, PALLET would cost the Swiss healthcare system an additional CHF155 million/year. Palbociclib plus letrozole cannot be considered cost-effective for the first-line treatment of patients with metastatic breast cancer in the Swiss healthcare system.

A cost-effectiveness analysis of trametinib plus dabrafenib as first-line therapy for metastatic BRAF V600-mutated melanoma in the Swiss setting.

BACKGROUND: The treatment of patients with metastatic melanomas that harbour BRAF V600E or V600K mutations with trametinib plus dabrafenib appears to be superior to treatment with vemurafenib alone. This treatment regimen is likely to become available in Switzerland in the near future. OBJECTIVES: To determine the cost-effectiveness of trametinib plus dabrafenib. METHODS: A Markov cohort simulation was conducted to model the clinical course of typical patients with metastatic melanoma. Information on response rates, clinical condition and follow-up treatments were derived and transition probabilities estimated based on the results of a clinical trial that compared treatment with trametinib plus dabrafenib vs. vemurafenib alone. RESULTS: Treatment with trametinib plus dabrafenib was estimated to cost an additional CHF199 647 (Swiss francs) on average and yield a gain of 0·52 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio of CHF385 603 per QALY. Probabilistic sensitivity analyses showed that a willingness-to-pay threshold of CHF100 000 per QALY would not be reached at the current US price of trametinib. CONCLUSIONS: The introduction of trametinib in Switzerland at US market prices for the treatment of metastatic BRAF V600-mutated melanoma with trametinib plus dabrafenib is unlikely to be cost-effective compared with vemurafenib monotherapy. A reduction in the total price of the combination therapy is required to achieve an acceptable cost-effectiveness ratio for this clinically promising treatment.

Stringent adherence to a cytomegalovirus-prevention protocol is associated with reduced overall costs in the first 6 months after kidney transplantation.

BACKGROUND: We previously documented that a stringent implementation of a preemptive cytomegalovirus (CMV) prevention protocol reduced the number of CMV disease episodes after kidney transplantation, when compared with a routine preemptive protocol. The impact on overall costs was assessed. METHODS: Cost comparisons were made for inpatient and outpatient costs and overall costs, using costs provided by the financial department. Variables were analyzed using the Wilcoxon rank-sum test. A multivariable global linear model evaluated the effect of all co-variables on cost differences. In Cohort 1 (n = 84), 74% were followed with a standard CMV preemptive protocol, and 26% received prophylaxis. In Cohort 2 (n = 74), an intensified CMV surveillance protocol was applied in 74% of patients, and 26% were given prophylaxis. RESULTS: Overall, Cohort 1 had significantly higher treatment costs as compared with Cohort 2 (mean Swiss francs [CHF] 104,548 and CHF 76,983, respectively, P = 0.0005). Excluding patients who received prophylaxis reduced these costs to CHF 89,318 in Cohort 1 and CHF 73,652 in Cohort 2. Outcome between Cohort 1 and 2 was comparable. CONCLUSION: A stringent adherence to the CMV prevention protocol was associated with a significant reduction in overall costs. Whether this benefit is because of the demonstrated reduction in the rate of CMV disease needs to be assessed in a randomized trial.

Off-label use of anticancer drugs in eastern Switzerland: a population-based prospective cohort study.

PURPOSE: Prevalence data on the off-label use (OLU) of anticancer drugs are limited despite OLU being controversial for medical, pharmaco-economic, and ethical reasons. We therefore quantified and characterized the OLU of anticancer drugs and compared OLU based on the national drug label with international treatment recommendations. METHODS: We prospectively collected data on patients receiving systemic anticancer therapy between October and December 2012 at hospitals affiliated with the Eastern Switzerland Oncology Network. Individual data on patient characteristics, tumor disease, and systemic treatment were collected, and each individual treatment was compared with the national drug label and international treatment guidelines. RESULTS: A total of 985 consecutive patients receiving 1,737 anticancer drug treatments were included in the study. Overall, 32.4 % of all patients received at least one off-label drug, corresponding to 27.2 % of all anticancer drugs administered. Major reasons for OLU were the lack of approval for the specific disease entity (15.7 %) and modified application of the anticancer drug (10 %). OLU that was unsupported by the current European Society for Medical Oncology (ESMO) treatment recommendations was rare (6.6 %) but higher for bevacizumab (29.6 %) due to its use in treating advanced ovarian cancer beyond the second-line setting and advanced breast cancer beyond the first-line setting and for lenalidomide (22.6 %) due to its use in treating Non-Hodgkin lymphoma. CONCLUSIONS: Based on data collected on our patient cohort, OLU of anticancer drugs in a European clinical setting applies to one-third of all cancer patients. ESMO-unsupported use of chemotherapies or molecularly-targeted drugs is rare, opposing concerns that the off-label use of newer anticancer drugs is a substantial clinical problem.

Addition of cetuximab to first-line chemotherapy in patients with advanced non-small-cell lung cancer: a cost-utility analysis.

BACKGROUND: Adding cetuximab to standard chemotherapy results in a moderate increase of overall survival in patients with advanced non-small-cell lung cancer (NSCLC), but the cost-effectiveness is unknown. MATERIALS AND METHODS: A Markov model was constructed based on the results of the First-Line ErbituX in lung cancer randomized trial, adding cetuximab to cisplatin-vinorelbine first-line chemotherapy in patients with advanced NSCLC. The primary outcome was the incremental cost-effectiveness ratio (ICER) of adding cetuximab, expressed as cost per quality-adjusted life year (QALY) gained, and relative to a willingness-to-pay threshold of €60 000/QALY. The impact of cetuximab intermittent dosing schedules on the ICER was also evaluated. RESULTS: Adding cetuximab to standard chemotherapy leads to a gain of 0.07 QALYs per patient at an additional cost of €26 088. The ICER for adding cetuximab to chemotherapy was €376 205 per QALY gained. Intermittent cetuximab dosing schedules resulted in ICERs per QALY gained between €31 300 and €83 100, under the assumption of equal efficacy. CONCLUSIONS: From a health economic perspective, the addition of cetuximab to standard first-line chemotherapy in patients with epidermal growth factor receptor-expressing advanced NSCLC cannot be recommended to date, due to a high ICER compared with other health care interventions. Treatment schedules resulting in more favorable cost-utility ratios should be evaluated.

Trastuzumab beyond progression: a cost-utility analysis.

BACKGROUND: The continuation of trastuzumab beyond progression in combination with capecitabine as secondary chemotherapy for HER2-positive metastatic breast cancer (MBC) prolongs progression-free survival without a substantial increase in toxicity. PATIENTS AND METHODS: A Markov cohort simulation was used to follow the clinical course of typical patients with MBC. Information on response rates and major adverse effects was derived, and transition probabilities were estimated, based on the results of the Breast International Group 03-05 clinical trial. Direct costs were assessed from the perspective of the Swiss health care system. RESULTS: The addition of trastuzumab to capecitabine is estimated to cost on average an additional of €33,980 and to yield a gain of 0.35 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio of €98,329/QALYs gained. Probabilistic sensitivity analysis showed that the willingness-to-pay threshold of €60,000/QALY was reached in 12% of cases. CONCLUSION: The addition of trastuzumab to capecitabine in MBC patients is more expensive than what is typically regarded as cost-effective but falls within the value ranges found for established regimens in the treatment of MBC.

Atypical cells in effusions: diagnostic value of cell image analysis combined with immunocytochemistry.

The reliable identification of tumor cells in populations of atypical cells occurring in body cavity effusions is a well-known diagnostic problem. In order to improve tumor cell detection and to predict disease progression, we developed a cell scoring strategy based on a combination of DNA cytophotometry and immunocytochemistry. For this purpose, morphologically atypical cells obtained from 33 effusion samples were submitted to DNA content analysis and tested for Ber-EP4 immunoreactivity. It turned out that elevated DNA content alone has a low specificity (true negative ratio) and sensitivity (true positive ratio) in predicting disease outcome, whereas Ber-EP4 immunoreactivity alone has a high specificity (100%) but a low sensitivity (56%). In contrast, the use of a scoring system combining the two techniques and relating scores to the previous disease state and the cytomorphology of the atypical cells results in highly specific and sensitive prediction of the disease outcome. We therefore suggest that this approach is a valuable tool for reliably identifying tumor cells in effusions containing populations of cytologically suspect cells.

Cyclosporine resistant effector cells in rabbit skin allografts.

Histoincompatible skin grafts in rabbits treated with cyclosporine can permanently engraft but show a transient mononuclear cellular infiltrate. This transient cyclosporine-resistant infiltrate consists of cells which are sensitive to steroids, radiation and cryopreservation. They have the same ACM-1 phenotype and the same characteristics as cyclosporine-sensitive cells.

B/T cell ratio of rabbit peripheral blood lymphocytes. Influence of separation technique on results.

Spontaneous in vitro T cell rosette formation at room temperature leading to enrichment of B cells has been reported. We tested 10 individual New Zealand White rabbits sequentially, separating the lymphocytes either at room temperature or at 37 degrees C. T cells are lost constantly at room temperature but to a lesser extent at 37 degrees C. The determination of the yield of lymphocytes after Ficoll separation gives the best control for the accuracy of the results. If lymphocytes are separated at 37 degrees C and if the yield of lymphocytes is greater than 45%, the variation in T cells is small and their number is constant between 62 and 74%. These data show that the reported wide range of T cells in rabbit peripheral blood is due to methodological errors and not inherent in the rabbit.