Sunitinib, sorafenib, temsirolimus or bevacizumab in the treatment of metastatic renal cell carcinoma: a review of health economic evaluations.

Renal cell carcinoma (RCC) is the most prevalent kidney cancer and the 5-year overall survival figure in metastatic disease (mRCC) is about 10%. New targeted drugs (sunitinib, sorafenib, bevacizumab, temsirolimus) have shown activity in the treatment of mRCC, but they are all associated with a significant burden of cost. To support decision makers in their allocation of resources, costeffectiveness models are constructed to compare the costs and outcomes of anticancer therapy. This survey focuses on studies since 2003 exploring health economics in the treatment of metastatic and/or advanced RCC employing these new drugs. This paper summarizes the results, focuses on the level of evidence of these studies, compares the calculated cost-effectiveness ratios and makes suggestions for future studies. This review reveals costs per life years gained (LYG) or quality-adjusted life years (QALY) in the range of euro 22,648 to euro203,692, depending on whether the setting is first-line or second-line and drug used. When compared to the other agents, sunitinib has the best cost-effectiveness figure. Second-line therapy does not offer valid incremental cost-effectiveness ratios.

Trastuzumab in adjuvant breast cancer therapy. A model based cost-effectiveness analysis.

Trastuzumab has shown activity in early breast cancer patients that overexpress HER2. Significant resources have to be allocated to finance this therapy, underlining the need for cost-effectiveness analysis. A model was set up, societal costs were calculated and the discount rate was 3%. Life expectancy data were based on the literature and prolonged according to qualified guess (10% and 20% absolute improvement in overall survival (OS)). The comparator was the FEC(100) regimen. The median additional health care cost per patient treated was 33,597 euros. The yielding cost per life year gained (LYG) was 15,341 euros with a 20% improved OS and 35,947 euros with 10% improved OS. The corresponding net health care cost per quality adjusted life year (QALY) was 19,176 euros and 44,934 euros. Including all resource use the figures were 8148 euros and 30,290 euros per LYG. Sensitivity analyses documented survival gain, price of trastuzumab, production gain and discount rate to be the major factors influencing cost-effectiveness ratio. Trastuzumab is indicated cost effective in Norway.

Cetuximab in the treatment of metastatic colorectal cancer: a model-based cost-effectiveness analysis.

Cetuximab (Erbitux) has shown activity in patients with metastatic colorectal cancer (mCRC). To evaluate the cost-effectiveness of this drug combined with irinotecan in mCRC, a model-based cost-effectiveness analysis (CEA) was performed. Data on cetuximab obtained from Medline in December 2004 and from the 2004 ASCO-meeting were analyzed for life years gained (LYG) with regard to the use of this monoclonal antibody (MAb). Norwegian prices as of January 2005 were employed. The LYG ranged between 1.7 and 2.0 years. The median cost per patient treated was calculated to 34,256 Euro to 45,764 Euro yielding a cost per LYG in the range between 205,536 Euro and 323,040 Euro. Sensitivity analysis documented price of cetuximab and survival gain to be the major factors influencing the cost-effectiveness ratio. In conclusion, the analysis indicates cetuximab to be a promising, but very expensive antibody.

A monoclonal antibody against HER-2 (trastuzumab) for metastatic breast cancer: a model-based cost-effectiveness analysis.

BACKGROUND: The aim of this study was to evaluate the cost-effectiveness of trastuzumab in patients with metastatic breast cancer (MBC) in a model-based cost-effectiveness analysis (CEA). Trastuzumab has shown considerable activity in patients with MBC that overexpress HER2. However, significant resources have been allocated to finance this new therapy. Due to ever increasing pressures on health care budgets, economic evaluations are requested in order to compare health effects with costs. METHODS: All available data on trastuzumab in MBC presented at the San Antonio breast cancer conference in late 2003 and all data on Medline in December 2003 were analysed for life years (LY) gained and quality of life (QoL) with regard to the use of this new monoclonal antibody. Randomised studies comparing standard chemotherapy, with or without trastuzumab, were focused. The costs were calculated according to Norwegian prices as of January 2003. RESULTS: The LY gained ranged between 0.3 and 0.7 years. The median cost per patient treated was 44 196 yielding costs per life year saved in the range 63 137-162 417 depending on survival gain and discount rate employed. A sensitivity analysis documented the price of trastuzumab and the survival benefit the two major factors influencing the cost-effectiveness ratio. CONCLUSION: The economic evaluation indicates that trastuzumab is not cost effective in metastatic breast cancer. Reduced drug costs and/or improved survival may alter the conclusion.

Ralitrexed (Tomudex) or Nordic-FLv regimen in metastatic colorectal cancer: a randomized phase II study focusing on quality of life, patients' preferences and health economics.

Raltitrexed (Tomudex) is proven effective in metastatic colorectal cancer. Between 1998-2000, 25 patients were included in a randomized phase II study comparing raltitrexed (13 patients) and the Nordic FLv regimen (12 patients). 23 patients were evaluable for response. The overall response rate was 2/12 (1 CR, 1 PR) in the raltitrexed arm and 1/11 (1 CR) in the Nordic FLv arm, respectively. There was no difference in overall survival (raltitrexed--14.7 months, Nordic FLv--15.4 months). 23 patients were evaluable for Quality of Life (QoL) analysis. 23/25 and 17/21 questionnaires (EORTC QLQ C-30) were returned at baseline and first evaluation. Raltitrexed tended to be the most toxic regimen, when looking at nausea and vomiting, appetite loss, diarrhea and global QoL. However, most patients (65%) recommended the raltitrexed treatment schedule. The total treatment cost was equal in both arms (about 6,800 EURO/patient) and the hospital/hospital hotel stay costs accounted for more than half of it.

Goserelin (Zoladex) or orchiectomy in metastatic prostate cancer? A quality of life and cost-effectiveness analysis.

BACKGROUND: We have today two treatment alternatives (orchiectomy or LHRH-analogue) in metastatic prostate cancer offering the same expectations of survival. This study documents the quality of life (QoL) and cost-effectiveness of these alternatives. PATIENTS AND METHODS: 65 consecutive patients treated at the University Hospital of Tromsø (UHT), Norway, between 1994 and 1999 were registered. At evaluation, 45 patients (LHRH-analogue--15 patients, orchiectomy--30 patients) were alive and included in the QoL-study (EORTC QLQ C-30, QoL 15D). 45 patients were followed-up at the UHT and included in the cost-analysis. Costs were calculated for a 36-month interval and converted to British pounds (1 Pound = 13 NOK). A 5% d.r. was employed. RESULTS: The mean QoL (15D) was 76.4 (orchiectomy) and 72 (LHRH) (0-100 scale). Constipation, urinating problems, fatigue, pain and loss of sexual functioning were the dominant symptoms. The treatment costs per patient treated were 8,895 Pounds (orchiectomy) and 10,937 Pounds (LHRH-analogue). The crossover in cost was located at 25 months. A sensitivity analysis varying discount rate (0-10%), drug charges (25-50% off) and treatment time (12-18 months) did not alter the conclusion. CONCLUSION: Orchiectomy is the treatment of choice when life expectancy is more than two years.

Screening for metastatic disease in newly diagnosed breast cancer patients. What is cost-effective?

BACKGROUND: Significant health care resources are today spent on diagnosing and treatment of early breast cancer. MATERIALS AND METHODS: 98 consecutive patients referred to our oncological unit between January 1997 and June 1998 underwent an evaluation programme including thoracic X-ray, liver and bone scan and blood test. When findings suspected for metastatic disease were revealed, further examinations (CT-scan, MRI) were performed. RESULTS: Whereas the screening programme disclosed four cases (4%) of distant metastasis, several patients had to suffer the psychological distress of false positive results. One in three suspicious thoracic X-rays, two in two liver scans and 18 out of 21 suspected bone scans were concluded false positive in terms of metastatic disease. A screening programme including blood test and thoracic X-ray alone, would have mis-classified one out of 98 patients. CONCLUSION: This study indicated thoracic X-ray and blood test as being sufficient and 110 Pounds per patient screened could be saved.

Health, life and disability insurance and hereditary risk for breast or colorectal cancer.

Fear of insurance discrimination affecting the insurance-seeker and family has been reported as the singlemost important reason why individuals choose not to undergo genetic testing. The eleven health insurers operating on the Norwegian market were mailed a questionnaire asking them to list their insurance products and evaluate two individuals' requests for insurance. The requests were constructed in order to illustrate a high genetic risk for (a) colorectal (HNPCC) and (b) breast cancer (BRCAI/BRCA2), respectively. Nine out of 11 insurers responded. While no restriction was documented concerning risk of BRCA1/BRCA2 and life insurance or disability pension, the premium paid by persons with susceptibility to HNPCC varied between the different insurers from standard to raised premiums. The product 'critical disease' insurance was refused or obtained at normal or raised premiums in both cases, depending on the insurer in question. On examining personal indemnity insurance, we found that the BRCA1/BRCA2-risk individual was offered insurance at the standard premium, whereas HNPCC-risk individuals were offered a standard or raised premium. Only the major Norwegian insurer is in fact diverging in its policies.

Adjuvant cyclophosphamide, methotrexate, fluorouracil (CMF) in breast cancer--is it cost-effective?

Adjuvant chemotherapy (ACT) may expose patients to morbidity, with little gain in outcome. Treatment with CMF (cyclophosphamide, methotrexate, fluorouracil) has been the standard ACT in several countries for decades. In this model, efficacy, tolerability and quality of life data from the English-language literature were incorporated with Norwegian standard ACT practice and cost data in a cost-effectiveness/cost-utility approach. The CMF efficacy was calculated as 2.45 years saved per patient treated. The quality of life was assumed diminished by 0.33 (0-1 scale) for 6 months and the life years gained were valued Q = 0.86. An 85% dose intensity was employed, one British pound ( 1) was calculated as 12 NOK and a 5% discount rate was used. The total cost of adjuvant CMF, including amounts spent on drugs, administration, travelling and production loss, was calculated to 2365- 6253, depending on the method chosen. Money spent on drugs alone constituted 13-34%. The cost per life year saved was measured as 2170- 5737. A cost-utility approach revealed a cost per quality-adjusted life year (QALY) of 2973- 7860. Adjuvant CMF in breast cancer is cost-effective in Norway.

[Should the community pay for hospitalized patients waiting for transfer to nursing homes?]. / Kommunal betaling for ferdigbehandlede pasienter i sykehus?

Many hospital patients are on waiting lists for transferral to nursing homes. In a retrospective study, all patients (n = 75) hospitalised at the Department of Oncology, University Hospital of Tromsø until their death and all patients (n = 20) transferred to nursing homes from the same department during a 23-month period were registered. The duration of hospitalisation was 1-111 days (median 10 days) for the first group and 1-39 days (median 8 days) for the second group. 23 out of 32 patients (72%) hospitalised more than 14 days were from the city of Tromsø. This city and other municipalities should be required by law to pay the hospital for patients on waiting list for nursing homes. Today, 4 out of 16 major Norwegian hospitals have such arrangements.

Intracavity fractionated balloon brachytherapy in glioblastoma.

In order to reduce hospitalisation time for patients receiving postoperative radiotherapy a phase I-II study of intracavity balloon brachytherapy was instituted. An indwelling balloon catheter was implanted during the closing phase of the initial operation. Starting on the second or third postoperative day the catheter was afterloaded with a high dose rate isotope via a remotely controlled afterloading system. The treatment consisted of 10-12 fractions over a period of 5-6 days, with each treatment session requiring approximately 15 minutes. No external beam radiation was given. Forty-four newly diagnosed patients were treated. A total dose of either 60 Gy (33 patients) or 72 Gy (11 patients) was given. The overall median survival was 11.7 months, (range 2.7-50.9). The treatment was well tolerated and none of the applicators were removed prematurely. The total median hospital stay for this group of patients was significantly reduced compared to more conventional protocols. This study indicates that intracavity high dose rate balloon brachytherapy can achieve survival rates equivalent to those of conventional radiotherapy and is both cost and time efficient.

Breast cancer screening by mammography in Norway. Is it cost-effective?

BACKGROUND: Mammography screening is a promising method for improving prognosis in breast cancer. PATIENTS AND METHODS: In this economic analysis, data from the Norwegian Mammography Project (NMP), the National Health Administration (NMA) and the Norwegian Medical Association (NMA) were employed in a model for cost-effectiveness analysis. According to the annual report of the NMP for 1996, 60,147 women aged 50-69 years had been invited to a two-yearly mammographic screening programme 46,329 (77%) had been screened and 337 (0.7%) breast cancers had been revealed. The use of breast conserving surgery (BCS) was in this study estimated raised by 17% due to screening, the breast cancer mortality decreased by 30% and the number of life years saved per prevented breast cancer death was calculated 15 years. RESULTS: The cost per woman screened was calculated 75.4 Pounds, the cost per cancer detected 10.365 Pounds and the cost per life year (LY) saved 8.561 Pounds. A raised frequency of BCS, diagnosis and adjuvant chemotherapy brought two years forward, follow-up costs and costs/savings due to prevented breast cancer deaths were all included in the analysis. A sensitivity analysis documented mammography screening cost-effective in Norway when four to nine years are gained per prevented breast cancer death. CONCLUSION: Mammography screening in Norway looks cost-effective. Time has come to encourage national screening programmes.

Prevention of colorectal cancer: a cost-effectiveness approach to a screening model employing sigmoidoscopy.

BACKGROUND: Today, only carcinoma of the bronchus kills more people than colorectal cancer (CRC). However, CRC is both preventable and curable. In Norway, projects aiming to detect adenomas and early cancers by the screening of a population aged about 60 years employing sigmoidoscopy have been discussed. MATERIALS AND METHODS: In this study, a mathematical model was used to estimate the cost-effectiveness of a screening programme for colorectal polyps followed by polypectomy. A once-only sigmoidoscopy at age 60 followed by coloscopy in selected risk groups was suggested. Data from the English-language literature, the National Cancer Registry of Norway, and Statistics Norway were included. Norwegian cost data from the National Health Administration were also used. Costs of screening and those related to earlier diagnosis, and savings on health care and averted loss in production due to prevented CRCs were calculated. RESULTS: The basic cost per patient invited and screened (70% compliance) in the suggested programme was estimated at 81.7 Pounds and 116.7 Pounds, respectively. When gains due to prevented CRCs were included, the figures became 34.5 Pounds and 49.2 Pounds. The cost per life-year saved was calculated as 2,889 Pounds. This strongly indicates that screening for the early detection and prevention of CRC is one of the most cost-effective programmes in cancer. CONCLUSIONS: CRC screening according to the suggested programme appears to be cost-effective. Clear evidence that screening can reduce mortality from CRC should convince health-care policy makers that the time has come to encourage screening for colorectal cancer.

Lumpectomy or mastectomy? Is breast conserving surgery too expensive?

In the last decade, breast cancer patients have enjoyed an increase in breast conserving surgery (BCS). At present, modified radical mastectomy (MRM) and BCS offers equal expectations of survival. During the last few years, however, a drop in the frequency of BCS has been reported by several authors. Is this new trend due to economic concerns? To clarify the costs of breast cancer therapy (stage I and II), we review the literature and include a cost-utility and a cost-minimisation analysis comparing MRM and BCS. The treatment cost (per patient) of BCS and MRM in Norway was calculated at $9,564 and $5,596, respectively. Employing a quality of life gain in BCS of 0.03 (0-1 scale) and a 5% discount rate, the cost per QALY in BCS compared to MRM was $20,508. In cost-minimising analysis, BCS and mastectomy followed by reconstructive surgery had a cost of $10,748 and $8,538, respectively. This indicates that BCS remains within reasonable cost and should not be displaced by mastectomy on economic grounds.

Intrapleurally instilled mitoxantrone in metastatic pleural effusions: a phase II study.

Thirty cases (breast cancer-20 cases, malignant lymphoma-4 cases, different malignancies-6 cases) of histologically/cytologically verified malignant pleural effusion (MPE) in 29 patients were treated with intrapleurally instilled mitoxantrone (30 mg). The therapy was well tolerated. At evaluation, 25 patients had died of progressive disease. The median survival was 3 months (range 0.3-21.3 months). There were 26 responders (12 complete responses (CR), 14 partial responses (PR)), whereas 4 patients relapsed and 3 of these had an early relapse (within 3 months). Patients achieving PR or CR had a low risk (15%) of treatment failure. Five patients were subjected to a pharmacokinetic evaluation. This demonstrated rapidly declining plasma and pleural exudate levels of mitoxantrone within the first 6 hours. At 24 hours after instillation, mitoxantrone was only detected in circulating mononuclear cells. This study shows that mitoxantrone is efficacious in the treatment of MPE, and may represent a cost-effective alternative.

[Hodgkin disease treated at the Tromsø regional hospital 1985-93. Diagnosis, treatment, prognosis, quality of life and costs of a decentralized treatment]. / Hodgkins sykdom behandlet ved Regionsykehuset i Tromsø 1985-93. Diagnostikk, behandling, prognose, livskvalitet og kostnad ved en regionalisert behandling.

Between 1985-93, 55 patients were treated for Hodgkin's disease at the University Hospital of Tromsø. The median diagnostic delay was four months and a significant prolonged delay was connected with the lymphocyte predominance subgroup. The ChlVPP regimen was shown to be a risk factor for herpes zoster virus infection. The 5-year overall survival was 90%. The survivors experienced a low frequency of symptoms and a high level of functioning. The females reported a significant superior global quality of life and had a lower psychological distress and fatigue score than the males. The cost of one quality-adjusted life year (QALY) (production gains included and using a 10% discount rate) was estimated to be 1,651 pounds. This makes Hodgkin's disease one of the most cost-effective malignancies to treat.

Adjuvant chemotherapy (5-fluorouracil and levamisole) in Dukes' B and C colorectal carcinoma. A cost-effectiveness analysis.

BACKGROUND: Adjuvant chemotherapy (5-fluorouracil, levamisole) is now standard practice in the treatment of Dukes' B and C coloretal carcinoma (CRC), and this has increased the financial burden on health care systems world-wide. PATIENTS AND METHODS: Between 1993 and 1996, 95 patients in northern Norway were included in a national randomised CRC study, and assigned to surgery plus adjuvant chemotherapy or surgery alone. In April 1996, 94 of the patients were evaluable and 82 were still alive. The total treatment costs (hospital stay, surgery, chemotherapy, administrative and travelling costs) were calculated. A questionnaire was mailed to all survivors for assessment of the quality of their lives (QoL) (EuroQol questionnaire, a simple QoL-scale, global QoL-measure of the EORTC QLQ-C30), and 62 of them (76%) responded. RESULTS: Adjuvant chemotherapy in Dukes' B and C CRC raised the total treatment costs by 3,369 pounds. The median QoL was 0.83 (0-1 scale) in both arms. Employing a 5% discount rate and an improved survival of adjuvant therapy ranging from 5% to 15%, we calculated the cost of one gained quality-adjusted life-year (QALY) to be between 4,800 pounds and 16,800 pounds. CONCLUSION: Using a cut-off point level of 20,000 pounds per QALY, adjuvant chemotherapy in CRC appears to be cost-effective only when the improvement in 5-year survival is > or = 5%. Adjuvant chemotherapy does not affect short-term QoL.

A cost-effectiveness approach to the Norwegian follow-up programme in colorectal cancer.

BACKGROUND: Today, continued periodic follow-up of patients treated for colorectal cancer (CRC) seems often to be routine because of tradition, rather than its demonstrated value. Recently, the Norwegian Gastrointestinal Cancer Group (NGICG) has recommended a standard surveillance programme in this malignancy. In this protocol patients are suggested followed for four years with CEA monitoring, ultrasound of the liver, chest radiograph and colonoscopy at regular intervals. MATERIALS AND METHODS: In this study, the cost-effectiveness of this programme was addressed employing Norwegian cost data and data from the Cancer Registry of Norway. Clinical data from the existing English language literature was used in the analysis. RESULTS: The basic cost of the NGICG recommended programme was 1,232 Pounds per patient. Including extended investigation due to suspected relapse in 45% of cases, the figure raised to 1,943 Pounds per patient. The cost per life year saved was indicated to 9,525 Pounds-16,192 Pounds. The corresponding cost per quality adjusted life year (QALY) was indicated to 11,476 Pounds-19,508 Pounds. CONCLUSION: We conclude the NGICG recommended follow-up programme in CRC cost-effective. Excluding CEA monitoring may improve the cost-effectiveness.

[Breast cancer treated at the oncologic department, University Hospital in Tromsø 1986-94]. / Brystkreft behandlet ved Kreftavdelingen, Regionsykehuset i Tromsø 1986-94.

In the period 1986 to 94, 173 women who had had a lumpectomy or a mastectomy were treated with radiotherapy at the University Hospital of Tromsø. The median diagnostic delay was 2.4 months (range 0-98.6 months). Three out of four patients were operated on within two weeks of the diagnosis being made. About two thirds experienced a delay of more than six weeks from the operation to the start of radiotherapy treatment. The five-year overall survival rate in the mastectomy and postoperative radiotherapy group was 67%. Patients with estrogen receptor positive tumours had a better prognosis. Only 5% and 7% of all patients in our region in stages I and II had breast conserving surgery (BCS) during the study period (66 patients). The five-year overall survival rate in the BCS group was 77%. BCS raised the cost per patient by about 3,000 GBP compared to modified radical mastectomy (MRM). The cost per QALY using BCS as against MRM was about 12,000 GBP. We conclude that MRM should not be used instead of BCS merely for economical reasons.