Olaparib not cost-effective as maintenance therapy for platinum-sensitive, BRCA1/2 germline-mutated metastatic pancreatic cancer.

OBJECTIVE: To assess the cost-effectiveness and budget impact of olaparib as a maintenance therapy in platinum-responsive, metastatic pancreatic cancer patients harboring a germline BRCA1/2 mutation, using the Swiss context as a model. METHODS: Based on data from the POLO trial, published literature and local cost data, we developed a partitioned survival model of olaparib maintenance including full costs for BRCA1/2 germline testing compared to FOLFIRI maintenance chemotherapy and watch-and-wait. We calculated the incremental cost-effectiveness ratio (ICER) for the base case and several scenario analyses and estimated 5-year budget impact. RESULTS: Comparing olaparib with watch-and wait and maintenance chemotherapy resulted in incremental cost-effectiveness ratios of CHF 2,711,716 and CHF 2,217,083 per QALY gained, respectively. The 5-year costs for the olaparib strategy in Switzerland would be CHF 22.4 million, of which CHF 11.4 million would be accounted for by germline BRCA1/2 screening of the potentially eligible population. This would amount to a budget impact of CHF 15.4 million (USD 16.9 million) versus watch-and-wait. CONCLUSIONS: Olaparib is not a cost-effective maintenance treatment option. Companion diagnostics are an equally important cost driver as the drug itself.

Breast Cancer Assessment With Pulse-Echo Speed of Sound Ultrasound From Intrinsic Tissue Reflections: Proof-of-Concept.

PURPOSE: The aim of this study was to differentiate malignant and benign solid breast lesions with a novel ultrasound (US) technique, which measures speed of sound (SoS) using standard US transducers and intrinsic tissue reflections and scattering (speckles) as internal reference. MATERIALS AND METHODS: This prospective, institutional review board-approved, Health Insurance Portability and Accountability Act-compliant prospective comparison study was performed with prior written informed consent from 20 women. Ten women with histological proven breast cancer and 10 with fibroadenoma were measured. A conventional US system with a linear probe was used for SoS-US (SonixTouch; Ultrasonix, Richmond, British Columbia, Canada). Tissue speckle reflections served as a timing reference for the US signals transmitted through the breasts. Relative phase inconsistencies were detected using plane wave measurements from different angular directions, and SoS images with 0.5-mm resolution were generated using a spatial domain reconstruction algorithm. The SoS of tumors were compared with the breast density of a larger cohort of 106 healthy women. RESULTS: Breast lesions show focal increments ΔSoS (meters per second) with respect to the tissue background. Peak ΔSoS values were evaluated. Breast carcinoma showed significantly higher ΔSoS than fibroadenomas ([INCREMENT]SoS > 41.64 m/s: sensitivity, 90%; specificity, 80%; area under curve, 0.910) and healthy breast tissue of different densities (area under curve, 0.938; sensitivity, 90%; specificity, 96.5%). The lesion localization in SoS-US images was consistent with B-mode imaging and repeated SoS-US measurements were reproducible. CONCLUSIONS: Using SoS-US, based on conventional US and tissue speckles as timing reference, breast carcinoma showed significantly higher SoS values than fibroadenoma and healthy breast tissue of different densities. The SoS presents a promising technique for differentiating solid breast lesions.

A cost-effectiveness analysis of consolidative local therapy in oligometastatic non-squamous non-small cell lung cancer (NSCLC).

BACKGROUND: Novel systemic therapies have improved the prognosis of metastatic non-small cell lung cancer (NSCLC), but costs of some of these drugs are a matter of ongoing debate. More recently, local therapies (LT) such as radiotherapy and surgery have been suggested as additional treatment in oligometastatic NSCLC demonstrating an improved progression-free survival (PFS) in a phase II trial compared to maintenance chemotherapy (MC) alone. The aim of this analysis was to assess the cost-effectiveness of local therapies in oligometastatic NSCLC. METHODS: We constructed a Markov model comparing the cost-effectiveness of LT versus MC for oligometastatic NSCLC from the Swiss healthcare payer's perspective. Treatment specifications and PFS were based on the phase II trial (NCT01725165). Overall survival (OS) was inferred from a recent phase III trial. Utilities were taken from published data. Primary outcome was the incremental cost-effectiveness-ratio (ICER, costs in Swiss Francs (CHF) per quality-adjusted life-year (QALY) gained). RESULTS: PFS in the model was 3.8 months for MC and 11.4 months for LT (compared to 3.9 months and 11.9 months in the trial). OS in the model was 15.5 months in both arms. LT was cost-effective with a gain of 0.24 QALYs at an additional cost of CHF 9641, resulting in an ICER of CHF 40,972/QALY gained. Probabilistic sensitivity analyses demonstrated that LT was dominant or cost-effective at a willingness-to-pay threshold of CHF 100,000 per QALY in 61.7% of the simulations. CONCLUSIONS: LT may be cost-effective for selected patients with oligometastatic NSCLC responding to first-line systemic therapy.

Impact of a Surgical Sealing Patch on Lymphatic Drainage After Axillary Dissection for Breast Cancer: The SAKK 23/13 Multicenter Randomized Phase III Trial.

BACKGROUND: Several studies and a meta-analysis showed that fibrin sealant patches reduced lymphatic drainage after various lymphadenectomy procedures. Our goal was to investigate the impact of these patches on drainage after axillary dissection for breast cancer. METHODS: In a phase III superiority trial, we randomized patients undergoing breast-conserving surgery at 14 Swiss sites to receive versus not receive three large TachoSil® patches in the dissected axilla. Axillary drains were inserted in all patients. Patients and investigators assessing outcomes were blinded to group assignment. The primary endpoint was total volume of drainage. RESULTS: Between March 2015 and December 2016, 142 patients were randomized (72 with TachoSil® and 70 without). Mean total volume of drainage in the control group was 703 ml [95% confidence interval (CI) 512-895 ml]. Application of TachoSil® did not significantly reduce the total volume of axillary drainage [mean difference (MD) -110 ml, 95% CI -316 to 94, p = 0.30]. A total of eight secondary endpoints related to drainage, morbidity, and quality of life were not improved by use of TachoSil®. The mean total cost per patient did not differ significantly between the groups [34,253 Swiss Francs (95% CI 32,625-35,880) with TachoSil® and 33,365 Swiss Francs (95% CI 31,771-34,961) without, p = 0.584]. In the TachoSil® group, length of stay was longer (MD 1 day, 95% CI 0.3-1.7, p = 0.009), and improvement of pain was faster, although the latter difference was not significant [2 days (95% CI 1-4) vs. 5.5 days (95% CI 2-11); p = 0.2]. CONCLUSIONS: TachoSil® reduced drainage after axillary dissection for breast cancer neither significantly nor relevantly.

A Cost-Effectiveness Analysis of Nivolumab versus Docetaxel for Advanced Nonsquamous NSCLC Including PD-L1 Testing.

INTRODUCTION: Nivolumab (NIV) was recently approved in several countries for patients with pretreated advanced NSCLC. NIV is not cost-effective compared with docetaxel (DOC) for the treatment of squamous NSCLC. However, its cost-effectiveness for nonsquamous NSCLC and the consequences of programmed death ligand 1 (PD-L1) testing are unknown. METHODS: This literature-based health economic study used CheckMate-057 trial data to model the incremental cost-effectiveness ratio (ICER) of NIV versus DOC in the Swiss health care setting. The effect of PD-L1 positivity for patient selection was assessed. RESULTS: In the base case model, NIV (mean cost CHF66,208; mean effect 0.69 quality-adjusted life-years [QALYs]) compared with DOC (mean cost CHF37,618; mean effect 0.53 QALYs) resulted in an ICER of CHF177,478/QALY gained. Treating only patients with PD-L1-positive tumors (threshold ≥10%) with NIV compared with treating all patients with DOC produced a base case ICER of CHF124,891/QALY gained. Reduced drug price, dose, or treatment duration decreased the ICER partly below a willingness-to-pay threshold of CHF100,000/QALY. Health state utilities strongly influenced cost-effectiveness. CONCLUSIONS: Compared with DOC, NIV is not cost-effective for the treatment of nonsquamous NSCLC at current prices in the Swiss health care setting. Price reduction or PD-L1 testing and selection of patients for NIV on the basis of test positivity improves cost-effectiveness compared with DOC.

Cost effectiveness of cytotoxic and targeted therapy for metastatic breast cancer: a critical and systematic review.

Breast cancer is the leading cancer type diagnosed among women in Western countries. Despite great advances in cancer therapies, many of these patients develop non-curable metastases. The objective of cancer treatment in the metastatic setting is mainly to control symptoms and to prolong survival. The selection of the optimal chemotherapeutic regimen is affected by performance status, tumour biology, site and extent of the disease and the exposure to prior therapies. Recent developments in new kinds of cancer drugs have contributed not only to immense progress in clinical outcomes but also to dramatically increased treatment-related health costs. Cost-effectiveness analysis is a type of economic evaluation that compares costs and health outcomes of alternative intervention strategies in a systematic way. In this review, a systematic literature search was performed and the evidence on the cost effectiveness of conventional chemotherapy and targeted therapy for metastatic breast cancer was explored. Cost-effectiveness/-utility analysis of treatment regimens for metastatic breast cancer were identified using literature and reference searches (MEDLINE). Published reports on conventional and targeted cancer therapies were scrutinized and incremental cost-effectiveness ratios (ICERs) were abstracted. Furthermore, the quality of reporting, as well as methodological and modeling issues, were extensively discussed. From full-text article reviews, six cost-effectiveness analyses on conventional therapies and seven studies on targeted therapies were included. Eight analyses were conducted in European countries, three in the US and two in Canada. The economic models were primarily (69%) based on clinical trial data. Results from sensitivity analyses and study perspectives were reported by all studies. Discount rates were mentioned in five articles (39%). The methods of reporting costs and effects varied considerably, as did trial design across conventional chemotherapies, which made it difficult to compare those analyses. The pharmacoeconomic studies came to different conclusions. The actual clinical evidence does not suggest one conventional chemotherapy regimen as superior. Studies on cytotoxic agents showed mainly favourable cost-effectiveness ratios. Targeted therapies indicated both favourable and non-favourable ratios. Currently, trastuzumab is the only antibody-based targeted therapy that is established in the clinic for the metastatic setting.

Is cancer prevention ever going to be profitable?

Undoubtedly, the war on cancer is an expensive endeavour. It is estimated that, where data are available in Europe (e.g. Germany and France), cancer care accounts for a similar proportion of overall health-care expenditure to that in the USA, i.e. approximately 5%. Currently, no society can afford all of the potential cancer treatments for all the patients that could benefit from them. How the required resources should be provided is one of the great on-going debates, and different countries approach this problem in different ways. Additionally, the more we understand about the pathology, pathogenesis, diagnosis and treatment of cancer, the more options are created. Many of these options are new diagnostic tools and more effective treatments. Obviously these innovations, paired with an increasing patient pool, are leading to tremendous health-care expenditures, well surpassing current budgets. Hence, the question arises of how many resources should be devoted to the management of cancers, given that resources are scarce and many other fields and specialities are competing for these resources. This paper addresses the question of whether preventive measures in oncology eventually pay off.

Bevacizumab in combination with paclitaxel for HER-2 negative metastatic breast cancer: an economic evaluation.

The addition of bevacizumab to weekly paclitaxel as primary chemotherapy for HER-2 negative metastatic breast cancer (MBC) prolongs progression-free survival without a substantial increase of toxicity. 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 E2100 clinical trial. Direct costs were assessed from the perspective of the Swiss health system. The addition of bevacizumab to weekly paclitaxel is estimated to cost an additional 40,369euro and to yield a gain of 0.22 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio of 189,427euro/QALY gained. Probabilistic sensitivity analysis showed that the willingness-to-pay threshold of 60,000euro was never reached. The addition of bevacizumab to paclitaxel in MBC patients is expensive given the clinical benefit in terms of QALYs gained.

Impact of clinical pathways in surgery.

BACKGROUND: One strategy to reduce the consumption of resources associated to specific procedures is to utilize clinical pathways, in which surgical care is standardized and preset by determination of perioperative in-hospital processes. The aim of this prospective study was to establish the impact of clinical pathways on costs, complication rates, and nursing activities. METHOD: Data was prospectively collected for 171 consecutive patients undergoing laparoscopic cholecystectomy (n = 50), open herniorrhaphy (n = 56), and laparoscopic Roux-en-Y gastric bypass (n = 65). RESULTS: Clinical pathways reduced the postoperative hospital stay by 28% from a mean of 6.1 to 4.4 days (p < 0.001), while the 30-day readmission rate remained unchanged (0.5% vs. 0.45%). Total mean costs per case were reduced by 25% from euro 6,390 to euro 4,800 (p < 0.001). Costs for diagnostic tests were reduced by 33% (p < 0.001). Nursing hours decreased, reducing nursing costs by 24% from euro 1,810 to euro 1,374 (p < 0.001). A trend was noted for lower postoperative complication rates in the clinical pathway group (7% vs. 14%, p = 0.07). CONCLUSIONS: This study demonstrates clinically and economically relevant benefits for the utilization of clinical pathways with a reduction in use of all resource types, without any negative impact on the rate of complications or re-hospitalization.

Cost-effectiveness analysis of adding a quadrivalent HPV vaccine to the cervical cancer screening programme in Switzerland.

OBJECTIVE: Based on positive safety and efficacy data, a quadrivalent Human PapillomaVirus (HPV) vaccine has been approved in Switzerland to prevent HPV types 6, 11, 16 and 18 infections. The objective of this study was to explore the cost-effectiveness of an HPV vaccination in Switzerland. DESIGN AND METHODS: A Markov model of the natural history of HPV infection was adapted to the Swiss context and followed a hypothetical cohort of 41,200 girls aged 11 years over their lifetime. Main epidemiological and economic parameters were extracted from the literature. Two strategies were compared: conventional cytological screening only and HPV vaccination followed by conventional cytological screening. A coverage rate of 80% was used and the vaccine was assumed to provide a lifelong protection. Analyses were performed from the direct health care cost perspective including only direct medical costs. RESULTS: Compared to screening only, adding a quadrivalent HPV vaccine could prevent over lifetime 62% of cervical cancers and related deaths, 19% of Cervical Intraepithelial Neoplasia (CIN 1), 43% of CIN 2, 45% of CIN 3 and 66% of genital warts per cohort. Incremental cost-effectiveness ratios (ICER) were estimated to be CHF 45,008 per Life Year Gained (LYG) and CHF 26,005 per Quality Adjusted Life Year (QALY) gained. Sensitivity analyses demonstrated that the ICER was robust to all parameters, but was most sensitive to the need for a booster and discount rates. CONCLUSIONS: Compared to commonly accepted standard thresholds in Europe and other vaccination strategies implemented in Switzerland, adding a quadrivalent HPV vaccine alongside the current cervical cancer screening programme is likely to be cost-effective in Switzerland.

Pharmacotherapy of acute coronary syndromes: medical economics with an emphasis on clopidogrel.

Acute coronary syndromes account worldwide for a significant burden of hospital- and societal costs. Pharmacotherapy of acute coronary syndromes consists of a combined antithrombotic therapy. Remarkable therapeutic advances have been made with the introduction of glycoprotein IIb/IIIa receptor inhibitors, low molecular weight heparins and thienopyridines, such as clopidogrel. Based on positive clinical data of large randomized trials numerous cost studies have been undertaken to analyse the cost-effectiveness of these new drugs. Most of them are showing an acceptable level of cost-effectiveness for the new treatments. Taking all available cost-studies into account, we conclude that new antithrombotic treatments are cost-effective as long as their use is limited to selected patient populations.

Paclitaxel: cost-effectiveness in ovarian cancer.

Ovarian cancer accounts for a significant burden of healthcare costs worldwide. Therapy of this disease consists of a combined surgical and chemotherapeutic approach. Remarkable advances in chemotherapy have been made with the introduction of new agents such as paclitaxel. Based on positive clinical data from randomized trials, numerous cost studies have been undertaken to analyze the cost-effectiveness of paclitaxel. Reviewing all the available cost studies, the authors conclude that paclitaxel plus cisplatin treatment is cost effective. Paclitaxel demonstrated survival and utility gains in combination with cisplatin as first-line treatment in patients with Stage II-IV ovarian cancer compared with cyclophosphamide and cisplatin. Incremental costs of USD 6600-22,000 per life year gained are within an accepted range for new treatments.

Management and costs of treating lung cancer patients in a university hospital.

BACKGROUND: New diagnostic tools and emerging medications have significantly changed the existing medical treatment options for lung cancer over the last 5 years. However, the increase in healthcare costs in all developed societies has put the more economical treatments on centre stage. OBJECTIVE: To examine the patterns and costs of lung cancer management at a Swiss University hospital at which there is a focus on interdisciplinary treatment. PATIENTS AND METHODS: All patients encountered during 1998 at the University Hospital of Zurich (USZ) with any diagnosis of lung cancer were selected for this retrospective study. Medical and sociodemographic data were collected by medical chart review for a period beginning with the first contact and ending with the last follow-up examination up to 30 months afterwards. Costs were calculated by assessing all resources used by each patient, multiplied by a uniform average cost factor. Results are in euros at 1999 prices. RESULTS: The sample included 118 patients (72% male) with a mean age of 64.2 years (SD 9.8, range 34-85 years) and a mean smoking history of 45 pack-years (SD 31.8, range 0-13 pack-years). Eighty-nine percent of all patients showed histology of non-small cell lung cancer (NSCLC), whereas 11% showed small cell lung cancer (SCLC). Of the NSCLC patients, 27% were classified as stage I, 14% as stage II, 19% as stage IIIA, 11% as stage IIIB and 26% as stage IV disease. The overall survival rate after 1 year was 55% and after 2 years was 29%. Gender and health insurance status were not associated with overall survival. The median length of hospitalisation during the first year of treatment was 14 days (range 0-112 days). For the entire patient sample, the mean cost per patient was 19,408 euros (median 14,691 euros, range 1821-80,020 euros), 71% of which was due to the hospitalisation costs. The mean cost per NSCLC patient was 19,212 euros (median 14,511 euros, range 1821-80,020 euros) and for SCLC patients it was 20,992 euros (median 15,367 euros, range 5282-51,840 euros). CONCLUSION: This is the first study attempting to estimate the hospital cost of treatment for lung cancer patients in Switzerland and central Europe. The major part of the total cost was due to hospitalisation costs. Patients with advanced stages of lung cancer show the highest cost, mainly due to the costs of chemotherapy. We found that the distribution of total cost is asymmetric: a small number of patients with an excessively long hospital stay cause very high costs.