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Background: ARASENS was a randomized, double-blind, phase 3 trial comparing darolutamide + docetaxel + androgen deprivation therapy (ADT) with placebo + docetaxel + ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC)., Objective: To use clinical trial data from ARASENS to understand whether the addition of darolutamide to docetaxel + ADT leads to increased hospitalizations and to estimate the budget impact on the US health care system., Methods: We used mixed-effects negative binomial regression to estimate hospitalization and intensive care unit (ICU) admission rates and length of hospital stay (LoHS) counts. Hospitalization rates were estimated per treatment arm for the period during and after administration of docetaxel. Based on these estimates, a budget impact analysis evaluated the hospitalization costs (including ICU admissions) and standalone ICU hospitalization costs for the totality of the US population over a 5-year time horizon. The analysis compared a scenario without darolutamide vs one with darolutamide included in the US payer formulary. Hospitalization estimates were varied in a one-way sensitivity analysis., Results: The first 4 months of treatment (when patients were receiving docetaxel) were associated with increased hospitalizations across both arms. The addition of darolutamide was associated with a numerical reduction in the rate of hospitalization (per year) due to any reason both during docetaxel treatment (1.01 visits per year [95% CI = 0.82-1.20] vs 1.18 visits per year [95% CI = 0.96-1.41]) and after docetaxel treatment (0.28 visits per year [95% CI = 0.23-0.34] vs 0.33 visits per year [95% CI = 0.27-0.40]). Darolutamide was associated with a marginally longer LoHS per hospitalization compared with placebo (+1.90 days per year) both during and after docetaxel treatment. ICU admissions were low in the ARASENS data; admission rates were assumed to be the same during and after docetaxel treatment. ICU admission rate estimates were equivalent across arms (0.02 visits per year [95% CI = 0.01-0.03]). The budget impact per treated member per month represents a cost-neutral option after Year 5 with a cumulative budget impact of -$9.71., Conclusions: The addition of darolutamide to docetaxel + ADT was associated with a numerically lower rate of hospitalization but marginally longer LoHS compared with docetaxel + ADT alone. Darolutamide represents a cost-neutral alternative per treated member per month compared with docetaxel + ADT with regard to hospitalizations at the end of a 5-year time horizon.

Cabazitaxel is used to treat patients with metastatic castration-resistant prostate cancer progressing after docetaxel. It is prepackaged in 60 mg single-dose vials, a quantity much higher than the average prescribed dose, which leads to, substantial drug wastage (DW) and associated costs. To minimize DW we implemented a cost-saving, cohorting strategy where multiple patients scheduled to receive cabazitaxel (at a dose of 20mg/m 2 every 3 wks) were cohorted and treated on a single weekday whenever possible. Excess drug from each vial was then saved and used for subsequent patients treated on the same day. The drug cost with cohorting was calculated from the actual number of vials used, and the drug cost without cohorting was estimated by assumingthat one vial was used per treatment. The cost of DW was determined based on the amount of drug that was discarded. All cost calculations also accounted for the discount incentives offered by Sanofi-Aventis. Over a 3-yr period, 74 patients received 402 treatments of cabazitaxel. Multiple patients were treated on 67.4% of the treatment days, and grouping of three patients on one day saved one vial. The estimated total drug cost saved was $394 536 CAD (21.1%). Pending further studies on safety and efficacy, this strategy could potentially be adopted to mitigate DW for cabazitaxel and similarly for other oncology drugs. This would significantly decrease the overall financial burden on patients, institutions, and stakeholders. PATIENT SUMMARY: Cabazitaxel chemotherapy is associated with substantial drug wastage and associated costs. By cohorting patients scheduled to receive cabazitaxel on a single weekday, the total drug cost was decreased by $394 536 CAD (21.1%) over a 3-yr period. Similar strategies could be considered to overcome the prohibitory costs associated with drug wastage for cabazitaxel and other cancer drugs., (Copyright © 2020 European Association of Urology. All rights reserved.)

Cabazitaxel (25 mg/m 2 every 3 weeks) is the standard second-line chemotherapy for patients with metastatic castration-resistant prostate cancer previously treated with docetaxel. It is associated with a risk of neutropenic complications, which may be a barrier to its use in daily clinical practice, particularly in frail elderly patients. Here the authors reviewed key studies conducted with cabazitaxel (TROPIC, PROSELICA, AFFINITY, CARD and the European compassionate use program) and pilot studies with adapted schedules. Based on this review, the use of prophylactic granulocyte colony-stimulating factor from cycle 1 appears crucial to maximize the benefit-risk ratio of cabazitaxel in metastatic castration-resistant prostate cancer. Preliminary data with alternative schedules look promising, especially for frail patients. Results of the ongoing Phase III CABASTY trial (ClinicalTrials.gov: NCT02961257) are awaited.

Aims: Paclitaxel is a type of broad-spectrum anticancer drug in short supply. The price of acetyl-CoA (17 709 677·4 USD mol -1 ), which is the acetyl group donor for the enzymatic synthesis of the intermediate, baccatin Ⅲ, is still the bottleneck of the mass production of paclitaxel. This study reports a novel acetyl group donor, which could substantially reduce the cost of production., Methods and Results: In this study, a substrate spectrum with 14 kinds of representative acetyl-donor substitutes predicted by computer-aided methods was tested in a 10-deacetylbaccatin Ⅲ-10-O-acetyltransferase (DBAT) heterogeneous-expressed open-whole-cell catalytic system. The results of computer prediction and experimental analysis revealed the rule of the acetyl-donor compounds based on this substrate spectrum. N-acetyl-d-glucosamine (30·95 USD mol -1 , about 572 202-fold cheaper than acetyl-CoA) is selected as a suitable substitute under the rule. The yield when using N-acetyl-d-glucosamine as acetyl donor in open-whole-cell catalytic system was 2·13-fold of that when using acetyl-CoA. In the in vivo system, the yield increased 24·17%, which may indicate its cooperation with acetyl-CoA., Conclusion: The success of open-whole-cell synthesis and in vivo synthesis of baccatin Ⅲ by adding N-acetyl-d-glucosamine as acetyl substrate demonstrates that it is a useful substrate to improve the yield of baccatin Ⅲ., Significance and Impact of the Study: All these findings provided a potential acetyl-donor substitute for acetyl-CoA, as well as a low cost and efficient method of preparing paclitaxel through baccatin Ⅲ semi-synthesis., (© 2020 The Society for Applied Microbiology.)

Aims: Among patients diagnosed with prostate cancer, 10-20% will develop castration-resistant prostate cancer (CRPC) within 5 years; for 70%, CRPC will metastasize, mostly to the lungs and/or liver. We performed a cost-effectiveness model comparing abiraterone plus prednisone (ABI + PRD), cabazitaxel plus prednisone (CAB + PRD) and enzalutamide (ENZ) for visceral metastatic CRPC post-docetaxel therapy resistance. Methods: A three-state (Progression-Free, Progression, Death) lifetime Markov model was constructed to compare ABI + PRD, CAB + PRD, and ENZ from a United States healthcare payer perspective (2019 US$; discount rate 3%/yr.). Effectiveness was measured in life-years (LYs) and quality-adjusted life years (QALYs). Inputs included treatment costs, grade III/IV adverse events with incidence ≥5%, physician follow-up, lab and imaging tests. Phase III trial Kaplan-Meier curves were extrapolated to estimate overall survival and Progression-Free transition probabilities. Incremental cost-effectiveness ratios (ICERs) and utility ratios (ICURs), probabilistic sensitivity analyses (PSAs) and cost-effectiveness acceptability curves at willingness-to-pay (WTP) thresholds were estimated. Results: Models estimated 3-year overall survival rates of 1.3% for patients treated with ABI + PRD, 16.2% for CAB + PRD, and 13.2% for ENZ. Estimated Progression-Free rates at 1.5 years were 0.51% for ABI + PRD, 0.27% for CAB + PRD, and 14.47% for ENZ. LYs and QALYs were 1.20 and 0.58 respectively for ABI + PRD, 1.48 and 0.56 for CAB + PRD, and 1.58 and 0.79 for ENZ. Total treatment costs were: $115,433 for ABI + PRD, $85,337 for CAB + PRD and $109,213 for ENZ. CAB + PRD and ENZ dominated ABI + PRD due to higher LYs gained. Incremental QALYs for ENZ vs. CAB + PRD were larger than incremental LYs. The ICUR for ENZ was $103,674/QALY compared to CAB + PRD. Conclusions: This analysis found ENZ provided greater LYs and QALYs than both ABI + PRD and CAB + PRD, at a lower cost than ABI + PRD, but at a higher cost compared to CAB + PRD. For patients with visceral mCRPC after docetaxel therapy resistance, ENZ was cost-effective 92% of the time with a WTP threshold of $100,000/QALY.

Natural production of anti-cancer drug taxol from Taxus has proved to be environmentally unsustainable and economically unfeasible. Currently, bioengineering the biosynthetic pathway of taxol is an attractive alternative production approach. 10-deacetylbaccatin III-10-O-acetyl transferase (DBAT) was previously characterized as an acyltransferase, using 10-deacetylbaccatin III (10-DAB) and acetyl CoA as natural substrates, to form baccatin III in the taxol biosynthesis. Here, we report that other than the natural acetyl CoA (Ac-CoA) substrate, DBAT can also utilize vinyl acetate (VA), which is commercially available at very low cost, acylate quickly and irreversibly, as acetyl donor in the acyl transfer reaction to produce baccatin III. Furthermore, mutants were prepared via a semi-rational design in this work. A double mutant, I43S/D390R was constructed to combine the positive effects of the different single mutations on catalytic activity, and its catalytic efficiency towards 10-DAB and VA was successfully improved by 3.30-fold, compared to that of wild-type DBAT, while 2.99-fold higher than the catalytic efficiency of WT DBAT towards 10-DAB and Ac-CoA. These findings can provide a promising economically and environmentally friendly method for exploring novel acyl donors to engineer natural product pathways.

Purpose: Breast cancer is the most common malignancy among women in Mexico. A large proportion of Mexican patients present with advanced disease, and 25% have HER2-positive tumors. We performed a cost-effectiveness analysis of different sequencing strategies of HER2-targeted agents in Mexico according to various payer perspectives., Methods: A Markov model was constructed to evaluate the cost-effectiveness of four different HER2-targeted treatment sequences among patients with HER2-positive metastatic breast cancer treated in Mexico according to three public and one private payer perspectives. Patients were followed weekly over their remaining life expectancies within the model. Health states considered were progression-free survival (PFS) 1st-3rd lines, and death. Transition probabilities between states were based on published trials. Cost data were obtained from official publications from Mexican healthcare institutions. The evaluated outcomes were PFS, OS, costs, QALYs, and incremental cost effectiveness ratio (ICER)., Results: In the public payer perspective, sequences containing pertuzumab or T-DM1 were not cost-effective when compared with a sequence including the combination of trastuzumab/docetaxel as first line without subsequent T-DM1 or pertuzumab, even when utilizing alternate definitions for willingness to pay thresholds. In the private payer perspective, a sequence containing T-DM1 but not pertuzumab proved cost-effective at a lower clinical effectiveness., Conclusions: In Mexico, the use of at least three lines of trastuzumab in combination with other therapies, but not with pertuzumab or TDM-1, represents the most cost-effective option for patients covered by the public healthcare system, and this sequence should be made available for all patients.

The E3805 (CHAARTED) study found that docetaxel combined with androgen-deprivation therapy (ADT) significantly improved overall survival of patients with metastatic hormone-sensitive prostate cancer. This study aims to determine whether docetaxel combined with ADT is a cost-effective strategy for advanced prostate cancer in China. According to the E3805 study, two groups (docetaxel + ADT and ADT alone) and three health states [progression-free survival (PFS), progressive disease (PD) and death] were analysed in a Markov model. All medical costs were calculated from the Chinese societal perspective. Quality-adjusted life year (QALY) and incremental cost-effectiveness ratios (ICERs) were applied as the primary outcome. Overall, the addition of docetaxel was estimated to increase the cost by $12 816.93, with a gain of 0.48 QALY. Additionally, for patients with high-volume disease, the increased cost and effectiveness were $14 627.75 and 0.69 QALYs in docetaxel + ADT group versus the ADT alone group, and the ICER was $21 199.63 per QALY. These ICERs are far more than the commonly accepted willingness-to-pay (WTP) threshold of $20 301 per QALY in China. In spite of longer survival time, docetaxel combined with ADT is not a recommended cost-effective treatment for metastatic hormone-sensitive prostate cancer in the Chinese setting., (© 2016 John Wiley & Sons Ltd.)

Objectives: To describe rates of confirmed and suspected neutropenic sepsis (NS) and associated hospital resource utilisation in patients with non-small cell lung cancer (NSCLC) treated with docetaxel monotherapy following relapse after ≥1 line of chemotherapy in routine UK clinical practice., Materials and Methods: A multi-centre, retrospective, observational research study was conducted in seven centres across England and Wales. Adult patients with stage III/IV NSCLC initiated on docetaxel monotherapy between 2010 and 2016 in routine clinical practice (aged ≥18 years at initiation) following failure of first-line chemotherapy were eligible. Data were collected from hospital medical records between May 2016 and July 2016, on all episodes of confirmed or suspected NS related to docetaxel monotherapy, including patient characteristics. Episodes of confirmed NS were defined as documented absolute neutrophil count <1.0×10 9 /L, plus temperature >38°C or other signs/symptoms of sepsis, otherwise episodes were classified as suspected NS., Results: 121 patients were included (median age 65.5 years; 57.9% male; median 4.0 cycles of docetaxel; 19.8% treated with prophylactic granulocyte-colony stimulating factor). Episodes of confirmed or suspected NS were recorded in 21/121 (17.4%) patients (11 confirmed episodes in 11 [9.1%] patients and 11 suspected episodes in 10 [8.3%] patients). Resource utilisation data were available for 21/22 episodes; the mean length of stay for confirmed NS admissions (n=11) was 9.2 (SD: 9.2) days and for suspected NS admissions (n=10) was 4.7 (SD: 4.6) days. The most commonly prescribed treatment for NS was piperacillin/tazobactam therapy (46.5% of all documented treatments). The mean total costs of managing patients with confirmed NS (n=11) and suspected NS (n=9) were £3163 (SD: £2921) and £1790 (SD: £1585) per patient, respectively., Conclusion: Rates of confirmed NS in UK clinical practice were broadly similar to those reported in clinical trials; however, the burden of suspected NS, not routinely reported elsewhere, is also substantial., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Prostate cancer (PC) is the most common urogenital malignancy in older men and the second leading cause of death by cancer in men in Europe. Current therapeutic practice considers Androgen Deprivation Therapy (ADT) as first line treatment for clinically localized prostate cancer at high-risk, either locally advanced or metastatic. ADT can be achieved through orchiectomy (surgical castration), luteinizing hormone-releasing hormone (LHRH) agonists, or through complete androgen blockade (LHRH agonist combined with an anti-androgen). Docetaxel in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone-refractory metastatic prostate cancer. The CHAARTED and STAMPEDE clinical trials studied the effect of bringing forward the use of docetaxel added on to ADT in the context of hormone-sensitive patients. The CHAARTED clinical trial showed a significant increase in a variable with maximum relevance such as Overall Survival (OS), with a difference of 13.6 months between medians. There was also clinical benefit in the secondary variables: median time until castration-resistant disease or until clinical progression. In the STAMPEDE clinical trial, which included 39% of non-metastatic patients, a 10-month difference between medians was demonstrated in OS, and 17 months in the primary co-variable of Progression Free Survival. The most frequent adverse events were: neutropenia, febrile neutropenia, leucopenia, and general disorders such as asthenia, lethargy or fever. According to data from the CHAARTED and STAMPEDE studies, and the incremental cost of € 3 196.98 for adding on docetaxel to standard treatment, the estimated additional cost for each year of life gained is compatible with an incremental cost-effectiveness ratio between € 2 267.36 and € 3 851.78. In view of the efficacy and safety results, the proposed positioning is: to advance the use of docetaxel added to androgen deprivation therapy to first-line metastatic hormone-sensitive prostate cancer, regardless of metastatic volume, in those patients who meet the CHAARTED study criteria., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Introduction: The aim of our analysis was to assess the real-world cost-effectiveness of bevacizumab in addition to taxane treatment versus taxane monotherapy for HER2-negative metastatic breast cancer compared with the cost-effectiveness based on the efficacy results from a trial., Methods: A state transition model was built to estimate costs, life years (LYs) and quality-adjusted life years (QALYs) for both treatments. Two scenarios were examined: a real-world scenario and a trial-based scenario in which transition probabilities were primarily based on a real-world cohort study and the E2100 trial, respectively. In both scenarios, costs and utility parameter estimates were extracted from the real-world cohort study. Moreover, the Dutch health care perspective was adopted., Results: In both the real-world and trial scenarios, bevacizumab-taxane is more expensive (incremental costs of €56,213 and €52,750, respectively) and more effective (incremental QALYs of 0.362 and 0.189, respectively) than taxane monotherapy. In the real-world scenario, bevacizumab-taxane compared to taxane monotherapy led to an incremental cost-effectiveness ratio (ICER) of €155,261 per QALY gained. In the trial scenario, the ICER amounted to €278,711 per QALY gained., Conclusion: According to the Dutch informal threshold, bevacizumab in addition to taxane treatment was not considered cost-effective for HER2-negative metastatic breast cancer both in a real-world and in a trial scenario., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To estimate the healthcare costs and characteristics of docetaxel chemotherapy episodes of care for men with metastatic castration-resistant prostate cancer (mCRPC)., Methods: This study used the Medicare 5% sample and MarketScan Commercial (2010-2013) claims data sets to identify men with mCRPC and initial episodes of docetaxel treatment. Docetaxel episodes included docetaxel claim costs from the first claim until 30 days after the last claim, with earlier termination for death, insurance disenrollment, or the end of a 24-month look-forward period from initial docetaxel index date. Docetaxel drug claim costs were adjusted for 2011 generic docetaxel introduction, while other costs were adjusted to 2015 values using the national average annual unit cost increase., Results: This study identified 281 Medicare-insured and 155 commercially insured men, with 325 and 172 docetaxel episodes, respectively. The average number of cycles (unique docetaxel infusion days) per episode was 6.9 for Medicare and 6.3 for commercial cohorts. The average cost per episode was $28,792 for Medicare and $67,958 for commercial cohorts, with docetaxel drug costs contributing $2,588 and $13,169 per episode, respectively. The average cost per episode on docetaxel infusion days was $8,577 (30%) for Medicare and $28,412 (42%) for commercial. Non-docetaxel infusion day costs included $7,074 (25%) for infused or injected drugs for Medicare, $10,838 (16%) for commercial cohorts, and $6,875 (24%) and $9,324 (14%) for inpatient admissions, respectively., Limitations: The applicability is only to the metastatic castration-resistance clinical setting, rather than the metastatic hormone-sensitive setting, and the lack of data on the cost effectiveness of different sequencing strategies of a range of systemic therapies including enzalutamide, abiraterone, radium-223, and taxane chemotherapy., Conclusion: The majority of docetaxel episode costs in Medicare and commercial mCRPC populations were non-docetaxel drug costs. Future research should evaluate the total cost of care in mCPRC.

Objective: To estimate the cost-effectiveness of liver resection followed by adjuvant systemic therapy relative to systemic therapy alone for patients with breast cancer liver metastasis., Background: Data on cost-effectiveness of liver resection for advanced breast cancer with liver metastasis are lacking., Methods: A decision-analytic Markov model was constructed to evaluate the cost-effectiveness of liver resection followed by postoperative conventional systemic therapy (strategy A) versus conventional therapy alone (strategy B) versus newer targeted therapy alone (strategy C). The implications of using different chemotherapeutic regimens based on estrogen receptor and human epidermal growth factor receptor 2 status was also assessed. Outcomes included quality-adjusted life months (QALMs), incremental cost-effectiveness ratio, and net health benefit (NHB)., Results: NHB of strategy A was 10.9 QALMs compared with strategy B when letrozole was used as systemic therapy, whereas it was only 0.3 QALMs when docetaxel + trastuzumab was used as a systemic therapy. The addition of newer biological agents (strategy C) significantly decreased the cost-effectiveness of strategy B (conventional systemic therapy alone). The NHB of strategy A was 31.6 QALMs versus strategy C when palbociclib was included in strategy C; similarly, strategy A had a NHB of 13.8 QALMs versus strategy C when pertuzumab was included in strategy C. Monte-Carlo simulation demonstrated that the main factor influencing NHB of strategy A over strategy C was the cost of systemic therapy., Conclusions: Liver resection in patients with breast cancer liver metastasis proved to be cost-effective when compared with systemic therapy alone, particularly in estrogen receptor-positive tumors or when newer agents were used.

Background: With the approval of several new treatments for metastatic castration-resistant prostate cancer (mCRPC), budgetary impact is a concern for health plan decision makers. Budget impact models (BIMs) are becoming a requirement in many countries as part of formulary approval or reimbursement decisions. Cabazitaxel is a second-generation taxane developed to overcome resistance to docetaxel and is approved for the treatment of patients with mCRPC previously treated with a docetaxel-containing regimen., Objective: To estimate a 1-year projected budget impact of varying utilization rates of cabazitaxel as a second-line treatment for mCRPC following docetaxel, using a hypothetical U.S. private managed care plan with 1 million members., Methods: A BIM was developed to evaluate costs for currently available treatment options for patients with mCRPC previously treated with docetaxel. Treatments included in the model were cabazitaxel, abiraterone acetate, enzalutamide, and radium-223, with utilization rates derived from market research data. Medication costs were calculated according to published pricing benchmarks factored by dosing and duration of therapy as stated in the prescribing information for each agent. Published rates and costs of grade 3-4 adverse events were also factored into the model. In addition, the model reports budget impact under 2 scenarios. In the first base-case scenario, patient out-of-pocket costs were subtracted from the total cost of treatment. In the second scenario, all treatment costs were assumed to be paid by the plan., Results: In a hypothetical 1 million-member health plan population, 100 patients were estimated to receive second-line treatment for mCRPC after treatment with docetaxel. Using current utilization rates for the 4 agents of interest, the base-case scenario estimated the cost of second-line treatment after docetaxel to be $6,331,704, or $0.528 per member per month (PMPM). In a scenario where cabazitaxel use increases from the base-rate case of 24% to a hypothetical rate of 33%, the PMPM cost would decrease to $0.524, reflecting a cost saving of $0.004 PMPM and equating to incremental savings of $49,546, or $497 per patient per year (PPPY). In the second scenario, when out-of-pocket costs were not considered, the cost of second-line treatment after docetaxel was estimated as $6,733,594, or $0.561 PMPM. With a hypothetical increase in cabazitaxel use (24%-33%), the PMPM cost would decrease to $0.554, reflecting savings of $0.007 PMPM and equating to incremental savings of $86,136, or $864 PPPY. The primary driver of cost savings with increased cabazitaxel use was lower acquisition cost. One-way sensitivity analyses revealed that the model results were robust over a wide range of input values (utilization, prevalence, and population parameters)., Conclusions: In the presented BIM, an increase in cabazitaxel use is expected to result in modest cost savings to the health plan. Patient coinsurance savings may also be realized based on applicable Medicare Part B and Part D calculations. This BIM presents an objective, comprehensive, robust, and user-adaptable tool that health plans and medical decision makers may use to evaluate potential economic impact of formulary and reimbursement decisions., Disclosures: Research and analysis were funded by Sanofi US. The sponsor had the opportunity to review the final draft; however, the authors were responsible for all content and editorial decisions. Flannery, Drea, Hudspeth, and Miao are employees of Sanofi. Miao is an owner of stock in Sanofi. Corman, Gao, and Xue are employees of Pharmerit International and served as consultants to Sanofi during this study. All authors contributed to study design and data collection and analysis. The manuscript was written by Flannery, along with the other authors, and revised by all the authors.

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures cabazitaxel (Jevtana ® , Sanofi, UK) to submit evidence for the clinical and cost effectiveness of cabazitaxel for treatment of patients with metastatic hormone-relapsed prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the company's submission to NICE. Clinical evidence for cabazitaxel was derived from a multinational randomised open-label phase III trial (TROPIC) of cabazitaxel plus prednisone or prednisolone compared with mitoxantrone plus prednisone or prednisolone, which was assumed to represent best supportive care. The NICE final scope identified a further three comparators: abiraterone in combination with prednisone or prednisolone; enzalutamide; and radium-223 dichloride for the subgroup of people with bone metastasis only (no visceral metastasis). The company did not consider radium-223 dichloride to be a relevant comparator. Neither abiraterone nor enzalutamide has been directly compared in a trial with cabazitaxel. Instead, clinical evidence was synthesised within a network meta-analysis (NMA). Results from TROPIC showed that cabazitaxel was associated with a statistically significant improvement in both overall survival and progression-free survival compared with mitoxantrone. Results from a random-effects NMA, as conducted by the company and updated by the ERG, indicated that there was no statistically significant difference between the three active treatments for both overall survival and progression-free survival. Utility data were not collected as part of the TROPIC trial, and were instead taken from the company's UK early access programme. Evidence on resource use came from the TROPIC trial, supplemented by both expert clinical opinion and a UK clinical audit. List prices were used for mitoxantrone, abiraterone and enzalutamide as directed by NICE, although commercial in-confidence patient-access schemes (PASs) are in place for abiraterone and enzalutamide. The confidential PAS was used for cabazitaxel. Sequential use of the advanced hormonal therapies (abiraterone and enzalutamide) does not usually occur in clinical practice in the UK. Hence, cabazitaxel could be used within two pathways of care: either when an advanced hormonal therapy was used pre-docetaxel, or when one was used post-docetaxel. The company believed that the former pathway was more likely to represent standard National Health Service (NHS) practice, and so their main comparison was between cabazitaxel and mitoxantrone, with effectiveness data from the TROPIC trial. Results of the company's updated cost-effectiveness analysis estimated a probabilistic incremental cost-effectiveness ratio (ICER) of £45,982 per quality-adjusted life-year (QALY) gained, which the committee considered to be the most plausible value for this comparison. Cabazitaxel was estimated to be both cheaper and more effective than abiraterone. Cabazitaxel was estimated to be cheaper but less effective than enzalutamide, resulting in an ICER of £212,038 per QALY gained for enzalutamide compared with cabazitaxel. The ERG noted that radium-223 is a valid comparator (for the indicated sub-group), and that it may be used in either of the two care pathways. Hence, its exclusion leads to uncertainty in the cost-effectiveness results. In addition, the company assumed that there would be no drug wastage when cabazitaxel was used, with cost-effectiveness results being sensitive to this assumption: modelling drug wastage increased the ICER comparing cabazitaxel with mitoxantrone to over £55,000 per QALY gained. The ERG updated the company's NMA and used a random effects model to perform a fully incremental analysis between cabazitaxel, abiraterone, enzalutamide and best supportive care using PASs for abiraterone and enzalutamide. Results showed that both cabazitaxel and abiraterone were extendedly dominated by the combination of best supportive care and enzalutamide. Preliminary guidance from the committee, which included wastage of cabazitaxel, did not recommend its use. In response, the company provided both a further discount to the confidential PAS for cabazitaxel and confirmation from NHS England that it is appropriate to supply and purchase cabazitaxel in pre-prepared intravenous-infusion bags, which would remove the cost of drug wastage. As a result, the committee recommended use of cabazitaxel as a treatment option in people with an Eastern Cooperative Oncology Group performance status of 0 or 1 whose disease had progressed during or after treatment with at least 225 mg/m 2 of docetaxel, as long as it was provided at the discount agreed in the PAS and purchased in either pre-prepared intravenous-infusion bags or in vials at a reduced price to reflect the average per-patient drug wastage.

Objectives: This analysis aimed to evaluate the cost-effectiveness of pembrolizumab compared with docetaxel in patients with previously treated advanced non-squamous cell lung cancer (NSCLC) with PD-L1 positive tumors (total proportion score [TPS] ≥ 50%). The analysis was conducted from a US third-party payer perspective., Methods: A partitioned-survival model was developed using data from patients from the KEYNOTE 010 clinical trial. The model used Kaplan-Meier (KM) estimates of progression-free survival (PFS) and overall survival (OS) from the trial for patients treated with either pembrolizumab 2 mg/kg or docetaxel 75 mg/m 2 with extrapolation based on fitted parametric functions and long-term registry data. Quality-adjusted life years (QALYs) were derived based on EQ-5D data from KEYNOTE 010 using a time to death approach. Costs of drug acquisition/administration, adverse event management, and clinical management of advanced NSCLC were included in the model. The base-case analysis used a time horizon of 20 years. Costs and health outcomes were discounted at a rate of 3% per year. A series of one-way and probabilistic sensitivity analyses were performed to test the robustness of the results., Results: Base case results project for PD-L1 positive (TPS ≥50%) patients treated with pembrolizumab a mean survival of 2.25 years. For docetaxel, a mean survival time of 1.07 years was estimated. Expected QALYs were 1.71 and 0.76 for pembrolizumab and docetaxel, respectively. The incremental cost per QALY gained with pembrolizumab vs docetaxel is $168,619/QALY, which is cost-effective in the US using a threshold of 3-times GDP per capita. Sensitivity analyses showed the results to be robust over plausible values of the majority of inputs. Results were most sensitive to extrapolation of overall survival., Conclusions: Pembrolizumab improves survival, increases QALYs, and can be considered as a cost-effective option compared to docetaxel in PD-L1 positive (TPS ≥50%) pre-treated advanced NSCLC patients in the US.

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., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches. Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs). Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional $151,560 and $140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar ($152,229 and $141,838, respectively, per QALY gained). Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost, outcomes, and incremental cost-utility.

Purpose: The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab to docetaxel and trastuzumab (THP) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2) -overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of adding pertuzumab., Patient and Methods: We developed a decision-analytic Markov model to evaluate the cost effectiveness of docetaxel plus trastuzumab (TH) with or without pertuzumab in US patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost effectiveness expressed as an incremental cost-effectiveness ratio. One- and multiway deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions., Results: Modeled median survival was 39.4 months for TH and 56.9 months for THP. The addition of pertuzumab resulted in an additional 1.81 life-years gained, or 0.62 QALYs, at a cost of $472,668 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost effectiveness at a willingness to pay of $100,000 per QALY gained., Conclusion: THP in patients with metastatic HER2-positive breast cancer is unlikely to be cost effective in the United States., Competing Interests: Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article., (© 2015 by American Society of Clinical Oncology.)

Background: Prostate cancer is expected to account for approximately one quarter of all new diagnoses of cancer in American men in 2015. The cost of prostate cancer care is expected to reach $15.1 billion by the year 2020, up from $11.9 billion in 2010. Given the high burden of prostate cancer, health care payers are interested in quantifying the potential budget impact of new therapies., Objective: To estimate the budget impact of enzalutamide for the treatment of chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) from a U.S. payer perspective., Methods: A model was developed to assess the budget impact of enzalutamide for treatment of chemotherapy-naïve mCRPC patients in a hypothetical 1-million-member U.S. health plan over a 1-year time horizon. Comparators included abiraterone acetate, sipuleucel-T, radium Ra 223 dichloride, and docetaxel. Epidemiologic data, including National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) incidence rates, were used to estimate the number of chemotherapy-naïve mCRPC patients. Dosing, administration, duration of therapy, and adverse event rates were based on package inserts and pivotal studies. Drug costs were obtained from RED BOOK and Centers for Medicare & Medicaid Services (CMS) average sales price pricing files, costs of administration and monitoring from the CMS physician fee schedule, and adverse events from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project and published literature. Market shares were estimated for each comparator before and after adoption of enzalutamide. The incremental aggregate budget impact, per patient per year (PPPY), per patient per month (PPPM), and per member per month (PMPM), was calculated. One-way sensitivity analyses were performed., Results: In a population of 115 chemotherapy-naïve mCRPC patients, adopting enzalutamide had an annual incremental budget impact of $510,641 ($4,426 PPPY, $369 PPPM, and $0.04 PMPM). Results were most sensitive to enzalutamide drug cost, size of the chemotherapy-naïve mCRPC patient population, and enzalutamide adoption rate., Conclusions: Results indicate a modest 1-year budget impact of adopting enzalutamide for chemotherapy-naïve mCRPC patients, partly because of the cost offset of a moderate incidence of adverse events and lack of additional required monitoring.

Purpose: Febrile neutropenia (FN) during adjuvant chemotherapy is associated with morbidity, mortality risk, and substantial cost, and subsequent chemotherapy dose reductions may result in poorer outcomes. Patients at high risk of, or who develop FN, often receive prophylaxis with granulocyte colony-stimulating factors (G-CSF). We investigated whether different prophylaxis strategies with G-CSF offered favorable value-for-money., Methods: We developed a decision model to estimate the short- and long-term costs and outcomes of a hypothetical cohort of women with breast cancer receiving adjuvant taxotere + cyclophosphamide (TC) chemotherapy. The short-term phase estimated upfront costs and FN risks with adjuvant TC chemotherapy without G-CSF prophylaxis (i.e., chemotherapy dose reductions) as well as with secondary and primary G-CSF prophylaxis strategies. The long-term phase estimated the expected costs and quality-adjusted life years (QALYs) for patients who completed adjuvant TC chemotherapy with or without one or more episodes of FN., Results: Secondary G-CSF was associated with lower costs and greater QALY gains than a no G-CSF strategy. Primary G-CSF appears likely to be cost-effective relative to secondary G-CSF at FN rates greater than 28%, assuming some loss of chemotherapy efficacy at lower dose intensities. The cost-effectiveness of primary vs. secondary G-CSF was sensitive to FN risk and mortality, and loss of chemotherapy efficacy following FN., Conclusions: Secondary G-CSF is more effective and less costly than a no G-CSF strategy. Primary G-CSF may be justified at higher willingness-to-pay thresholds and/or higher FN risks, but this threshold FN risk appears to be higher than the 20% rate recommended by current clinical guidelines.

Docetaxel and cyclophosphamide (TC) is a widely used breast cancer adjuvant regimen. We sought to compare the rates of febrile neutropenia (FN) between patients receiving no primary prophylaxis (PP) and those receiving PP with either granulocyte-colony stimulating factor (G-CSF) or antibiotics. We also analyzed cost-effectiveness of TC with and without either G-CSF or antibiotics. Charts were reviewed of all 340 patients who received adjuvant TC between January 2008 and December 2012 at two major cancer centers. Rates of FN in the three groups - no PP, PP with G-CSF and PP with antibiotics were compared. A Markov model was constructed comparing cost-effectiveness of PP with G-CSF, PP with antibiotics, and secondary prophylaxis (SP) with G-CSF after an episode of FN in a previous cycle. Costs were based on actual resource utilization and supplemented by the published literature, adjusted to 2012 Canadian dollars. Of the 73 (21%) patients who did not receive any PP, 23 (32%) of patients developed FN. Of the 192 (57%) patients receiving PP with G-CSF alone, only two (1%; p < 0.0001) developed FN; and of the 53 (16%) receiving PP with antibiotics alone, six (11%; p < 0.01) developed FN. From a cost-standpoint, PP with G-CSF was less cost-effective than PP with antibiotics. The rate of FN with TC chemotherapy exceeds 30%, and American Society of Clinical Oncology guidelines recommend PP with G-CSF in this situation. PP with antibiotics is more cost-effective, and is a reasonable option in resource-limited settings or for patients who decline or do not tolerate G-CSF., (© 2015 Wiley Periodicals, Inc.)

Breast cancer is a global health concern. In fact, breast cancer is the primary cause of death among women worldwide and constitutes the most expensive malignancy to treat. As health care resources are finite, decisions regarding the adoption and coverage of breast cancer treatments are increasingly being based on "value for money," i.e., cost-effectiveness. As the evidence about the cost-effectiveness of breast cancer treatments is abundant, therefore difficult to navigate, systematic reviews of published systematic reviews offer the advantage of bringing together the results of separate systematic reviews in a single report. As a consequence, this paper presents an overview of systematic reviews of the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer to inform policy and reimbursement decision-making. A systematic review was conducted of published systematic reviews documenting cost-effectiveness analyses of breast cancer treatments from 2000 to 2014. Systematic reviews identified through a literature search of health and economic databases were independently assessed against inclusion and exclusion criteria. Systematic reviews of original evaluations were included only if they targeted breast cancer patients and specific breast cancer treatments (hormone therapy, chemotherapy, and targeted therapy only), documented incremental cost-effectiveness ratios, and were reported in the English language. The search strategy used a combination of these key words: "breast cancer," "systematic review/meta-analysis," and "cost-effectiveness/economics." Data were extracted using predefined extraction forms and qualitatively appraised using the assessment of multiple systematic reviews (AMSTAR) tool. The literature search resulted in 511 bibliographic records, of which ten met our inclusion criteria. Five reviews were conducted in the early-stage breast cancer setting and five reviews in the metastatic setting. In early-stage breast cancer, evidence about trastuzumab value differed by age. Trastuzumab was cost-effective only in women with HER2-positive breast cancer younger than 65 years and over a life-time horizon. The cost-effectiveness of trastuzumab in HER2-positive metastatic breast cancer yielded conflicting results. The same conclusions were reached in comparisons between vinorelbine and taxanes. In both early stage and advanced/metastatic breast cancer, newer aromatase inhibitors (AIs) have proved cost-effective compared to older treatments. This overview of systematic reviews shows that there is heterogeneity in the evidence concerning the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer. The cost-effectiveness of these treatments depends not only on the comparators but the context, i.e., adjuvant or metastatic setting, subtype of patient population, and perspective adopted. Decisions involving the cost-effectiveness of breast cancer treatments could be made easier and more transparent by better harmonizing the reporting of economic evaluations assessing the value of these treatments.

Objective: To evaluate the cost-effectiveness of abiraterone, cabazitaxel, and enzalutamide compared to placebo for treatment of metastatic castration-resistant prostate cancer., Material and Methods: A decision-tree model compared three treatment options for metastatic castration-resistant prostate cancer patients over 18 months from a societal perspective in 2012 USD. Chance nodes included baseline pain as a severity indicator, significant adverse effects (neutropenia, cardiac events, or seizures), and survival. Probabilities, survival rates, and health utilities were from clinical trials (COU-AA, TROPIC, and AFFIRM) and other published studies. Survival of enzalutamide was adjusted to match placebo groups across trials. Probabilistic sensitivity analyses, acceptability curves and net benefit calculations were performed., Results: Abiraterone was the most cost-effective of the treatments ($123.4 K/quality-adjusted life year) compared to placebo, enzalutamide was $437.6 K/quality-adjusted life year compared to abiraterone, and cabazitaxel was $351.9 K/quality-adjusted life year compared to enzalutamide. Enzalutamide and cabazitaxel were not cost-effective compared to placebo at $154.3 K/quality-adjusted life year and $163.2 K/quality-adjusted life year, respectively. Acceptability curves showed abiraterone was cost-effective 29.3% of the time with a willingness to pay threshold of $100 K. The model was sensitive to changes in cost of the drugs, life expectancy, and survival rate. Sensitivity analysis shows that enzalutamide can become the most cost-effective option if the price of the medication decreased by 26% and other drug costs remained the same., Conclusion: Based on the cost-effective analysis, and survival adjustments necessary to match placebo groups, we would recommend abiraterone for treatment of metastatic castration-resistant prostate cancer despite not quite falling under the usually accepted willingness to pay threshold. Further analysis should examine comparative survival across the three drugs., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Aim: To carry out a cost-minimization analysis including a comparison of the costs arising from first-line treatment by trastuzumab plus docetaxel versus trastuzumab plus paclitaxel in patients with metastatic breast cancer., Methods: All consecutive patients with human epidermal growth receptor 2-postive metastatic breast cancer who were treated at Besançon University Hospital and Saint Vincent private hospital between 2001 and 2010 by first-line therapy containing trastuzumab plus taxane were retrospectively studied. Economic analysis took into account costs related to drugs, hospitalization, and healthcare travel., Results: Progression-free survival difference between the two treatments was not significant (p = 0.65). First-line treatment by trastuzumab plus taxane was estimated at approximately €68,000 (p = 0.74). The drug costs represented around 70-75% of the total cost, mainly related to the use of trastuzumab., Conclusion: Our economic analysis shows that although the costs of the two trastuzumab plus taxane regimens are similar, they may contribute to the on-going debate about the availability and use of innovative chemotherapy drugs, in particular in human epidermal growth factor receptor 2-positive metastatic breast cancer with new therapies such as trastuzumab-DM1 and pertuzumab., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: Existing treatments for metastatic breast cancer (mBC) are often effective but can cause adverse events (AEs). This study aimed to identify AEs associated with chemotherapies commonly used in mBC treatment (phase 1) and to quantify the economic impact of these AEs (phase 2)., Materials and Methods: Patients in phase 1 had at least one claim for therapy for mBC, with at least one episode with single or multiple agents. The most common chemotherapy-related complications were identified using medical and pharmacy claims data. In phase 2, patients meeting study criteria were divided into four treatment cohorts by the line of treatment and chemotherapy received: first-line taxane-treated patients, second-line taxane-treated patients, first-line capecitabine-treated patients, and second-line capecitabine-treated patients. Average monthly AE-related health care costs per cohort were stratified by cost component. Total monthly costs per number of AEs were also calculated., Results: On average, patients in phase 1 (n = 1,551) had 2 episodes of treatment, with a mean duration of 131 days. The most frequently noted complications were anemia (50.7% of mBC treatment episodes), bilirubin elevation (26.4%), and leukopenia (24.8%). In phase 2, costs related to AEs were primarily driven by incremental inpatient, outpatient, and pharmacy costs. Increases in average monthly costs ranged from $854 (9.0%) to $5,320 (69.5%), according to cohort. Overall costs increased with increasing numbers of AEs., Conclusion: Chemotherapy-related AEs in patients with mBC are associated with a substantial economic burden that increases with the number of AEs reported., (©AlphaMed Press.)

Background: There have been recent important changes to adjuvant regimens and costs of taxanes for the treatment of early breast cancer, requiring a re-evaluation of comparative cost effectiveness. In particular, weekly paclitaxel is now commonly used but has not been subjected to cost-effectiveness analysis., Aim: Our aim was to estimate the cost effectiveness of adjuvant docetaxel and weekly paclitaxel versus each other, and compared with standard 3-weekly paclitaxel, in women aged ≥25 years diagnosed with regional breast cancer in New Zealand., Methods: A macrosimulation Markov model was used, with a lifetime horizon and health system perspective. The model compared 3-weekly docetaxel and weekly paclitaxel versus standard 3-weekly paclitaxel (E1199 regimen) in the hospital setting. Data on overall survival and toxicities (febrile neutropenia and peripheral neuropathy) were derived from relevant published clinical trials. Epidemiological and cost data were derived from New Zealand datasets. Health outcomes were measured with health-adjusted life-years (HALYs), similar to quality-adjusted life-years (QALYs). Costs included intervention and health system costs in year 2011 values, with 3% per annum discounting on costs and HALYs., Results: The mean HALY gain per patient compared with standard 3-weekly paclitaxel was 0.51 with weekly paclitaxel and 0.21 with docetaxel, while incremental costs were $NZ 12,284 and $NZ 4,021, respectively. The incremental cost-effectiveness ratio (ICER) of docetaxel versus 3-weekly paclitaxel was $NZ 19,400 (purchasing power parity [PPP]-adjusted $US 13,100) per HALY gained, and the ICER of weekly paclitaxel versus docetaxel was $NZ 27,100 ($US 18,300) per HALY gained. In terms of net monetary benefit, weekly paclitaxel was the optimal strategy for willingness-to-pay (WTP) thresholds >$NZ 27,000 per HALY gained. However, the model was highly sensitive to uncertainty around survival differences, while toxicity-related morbidity had little impact. Thus, if it was assumed that weekly paclitaxel and docetaxel had the same efficacy, docetaxel would be favoured over weekly paclitaxel., Conclusion: Both weekly paclitaxel and docetaxel are likely to be cost effective compared with standard 3-weekly paclitaxel. Weekly paclitaxel was the optimal choice for WTP thresholds greater than $NZ27,000 per HALY gained (PPP-adjusted $US 18,000). However, uncertainty remains around relative survival benefits, and weekly paclitaxel becomes cost ineffective versus docetaxel if it is assumed that the two regimens have equal effectiveness. Reduced uncertainty about the relative survival benefits may improve decision making for funding.

Objective: Breast cancer (BC) and metastatic breast cancer (MBC) are significant causes of deaths amongst women worldwide, including developing countries. The cost of treatment in the latter is even more of an issue than in higher income countries. ErbB2 overexpression is a marker of poor prognosis and the goal for targeted therapy. This study was aimed at evaluating the cost-effectiveness in Colombia of ErbB2+ MBC treatment after progression on trastuzumab., Methods: A decision analytic model was constructed for evaluating such treatment in a hypothetical cohort of ErbB2+MBC patients who progressed after a first scheme involving trastuzumab. The alternatives compared were lapatinib+capecitabine (L+C), and trastuzumab+a chemotherapy agent (capecitabine, vinorelbine or a taxane). Markov models were used for calculating progression-free time and the associated costs. Effectiveness estimators for such therapy were identified from primary studies; all direct medical costs based on national fees-guidelines were included. Sensitivity was analyzed and acceptability curves estimated. A 3 % discount rate and third-payer perspective were used within a 5-year horizon., Results: L+C dominated its comparators. Its cost-effectiveness ratio was COP $49,725,045 per progression-free year. The factors most influencing the results were the alternatives' hazard ratios and the cost of trastuzumab., Conclusion: Lapatinib was cost-effective compared to its alternatives for treating MBC after progression on trastuzumab using a Colombian decision analytic model.

Objectives: Most economic evaluations of chemotherapies for ovarian cancer patients have used hypothetical cohorts or randomized control trials, but evidence integrating real-world survival, cost, and utility data is limited., Methods: A propensity score-matched cohort of 6856 elderly (≥65 years) ovarian cancer patients diagnosed from 1991 to 2005 from the Surveillance, Epidemiology, and End Results-Medicare data cohort were included. Treatment regimens (i.e., no chemotherapy, platinum-based only, platinum plus taxane, and other nonplatinum) were identified in the 6 months postdiagnosis. Patients were followed until death or end of study (December 2006). Effectiveness was measured in quality-adjusted life-years (QALYs), and total health care costs were measured by using a payer's perspective (2009 US dollars). Methodological and statistical uncertainties were accounted by including alternative scenarios (for utility values) and net monetary benefit approach. Incremental cost-effectiveness ratios (ICERs) were calculated, and stratified analyses were performed by tumor stages and age groups., Results: On comparing the platinum-based group versus no chemotherapy, we found that the ICER was $30,073/QALY and $58,151/QALY for early- and late-stage disease, respectively, while other nonplatinum and platinum plus taxane groups were dominated (less effective and more costly). Similar results were found across alternative scenarios and age groups. For patients 85 years or older, platinum plus taxane, however, was not dominated by the platinum-based group, with an ICER of $133,892/QALY., Conclusions: Following elderly ovarian cancer patients over a lifetime using real-world longitudinal data and adjusting for quality of life, we found that treatment with platinum-based regimen was the most cost-effective treatment alternative., (© 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Published by International Society for Pharmacoeconomics and Outcomes Research (ISPOR) All rights reserved.)

Aim: To describe drugs used in the non-hormonal treatment of metastatic prostate cancer., Material: Bibliographical search was performed from the database Medline (National Library of Medicine, PubMed) and websites of the HAS and the ANSM. The search was focused on the characteristics, the mode of action, the efficiency and the side effects of the various drugs concerned., Results: The metabolic radiotherapy although under-used for this indication, kept a place at the beginning of the disease. Radium-223 chloride seems to have to occupy an important place in the coming years. The chemotherapy, the only recourse until very recently in the castration-resistant prostate cancer, must redefine its place partially. The denosumab provide an interesting alternative to bisphosphonates., Conclusion: The non-hormonal treatment of the metastatic disease of the prostate cancer is changing rapidly with the emergence of new molecules. Urologist must know perfectly these new drugs., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Cancer treatments have improved outcomes but access to medications is an issue around the world and especially so in low- and middle-income countries, such as India. Generic substitution may lead to significant cost savings. The author aimed to compare the cost and estimate potential cost savings per cycle, per patient, and for the country as a whole with generic substitution of frequently used chemotherapy drugs in the treatment of common cancers in India. Generic paclitaxel (Taxol), docetaxel (Taxotere), gemcitabine, oxaliplatin and irinotecan cost from 8.9% to 36% of their equivalent branded originator drug, resulting in cost savings of ~ Indian Rupees (INR) 11,000 to >INR 90,000 (USD 200-1600, Euro 160-1300) per cycle; and ~INR 50,000 to >INR 240,000 (USD 900-4300, Euro 700-3400) per patient. Overall, potential yearly savings for health systems in India were nearly INR 47 billion (~USD 843 million, Euro 670 million). In conclusion, generic substitution for frequently used chemotherapy drugs in the treatment of common cancers has an enormous potential to generate significant cost savings and increase access to cancer treatments in India and other low- and middle-income countries.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of cabazitaxel (Jevtana®, sanofi-aventis, UK) to submit evidence of its clinical and cost effectiveness for the second-line treatment of metastatic hormone-refractory prostate cancer (mHRPC). The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. Clinical evidence was derived from a multinational randomized open-label phase III trial of cabazitaxel plus prednisone or prednisolone in men with mHRPC that had progressed during or following treatment with docetaxel. The comparator was mitoxantrone plus prednisone or prednisolone. Use of cabazitaxel was associated with a statistically significant improvement in overall survival, median progression-free survival and time to tumour progression. However, it was also associated with an increased incidence of adverse events such as neutropenia. Utility data were based on interim results from the early access programme for cabazitaxel. Data were only available for a small number of patients with stable disease, resulting in great uncertainty as to the effect of cabazitaxel on quality of life. For their economic evaluation, the manufacturer estimated that the use of cabazitaxel was associated with an incremental cost of £74,908 per QALY gained. However, the ERG disagreed with the manufacturer over two key methodological points. The first concerned modelling and extrapolating survival; the second point was concerned with the choice of patient population. The ERG altered the manufacturer's evaluation to take into account these two points of disagreement. The resulting cost per QALY gained was £82,950. The NICE Appraisal Committee believed the analysis presented by the ERG to be more plausible, and likely to be an underestimate of the cost per QALY. They concluded that whilst the clinical effectiveness of cabazitaxel had been proven, it was not likely to represent a cost-effective use of NHS resources and so its use could not be recommended.

Taxanes have become effective therapies for patients with metastatic breast cancer (MBC); however, understanding the differences among them is important. Each of the taxanes currently approved for treating MBC has a unique formulation, which translates to differences in toxicity profiles and administration considerations. In this article, the rationale for the development of the taxanes paclitaxel, docetaxel, and nab-paclitaxel is reviewed from a historical perspective. The mechanisms of action, formulations, and indications of taxanes also are discussed. The impact of their formulations on clinical practice and patient care, particularly solvent-based versus novel solvent-free formulations, will be reviewed from the nursing perspective.

Introduction: Non-small cell lung cancer (NSCLC) is associated with high morbidity and mortality. Surgery is generally accepted as the first-line treatment in patients with advanced/metastatic NSCLC, followed by radiotherapy and chemotherapy as second-line treatments. Docetaxel or erlotinib are generally recommended as the first-line chemotherapy option. The objective of this review was to identify previously published economic evaluations in NSCLC for second- and later-line treatments in order to (i) determine common modelling approaches and (ii) establish the relative cost effectiveness of these treatments. An overview of model critique was also produced to identify common criticisms from health technology assessment (HTA) bodies on the models submitted., Methods: MEDLINE, Embase, EconLit, MEDLINE in Process(®) and NHS Economic Evaluation Database (NHSEED) were searched (database start-October 2011), along with proceedings from eight major conferences (2007-2011). National Institute for Health and Clinical Excellence (NICE), Scottish Medicines Consortium (SMC), Pharmaceutical Benefits Advisory Committee (PBAC) and Canadian Agency for Drugs and Technologies in Health (CADTH) websites and the International Network of Agencies for Health Technology Assessment (INAHTA) database were also searched for appraisals in second- or later-line NSCLC. All published studies and HTA appraisals that reported economic evaluations of interventions used in current clinical practice as second- or later-line treatment in patients with advanced/metastatic NSCLC were included. Only studies in English were considered for inclusion. Studies which met the eligibility criteria after the screening of full-text articles were extracted by a reviewer and checked by a second party. Where multiple publications were identified describing a single study, the extracted data were compiled into one entry., Results: A total of 29 studies were included which clearly evaluated second-line or later-line regimens. Most studies were either cost-effectiveness or cost-utility evaluations. Three-state transition Markov models were frequently used in cost-effectiveness and cost-utility evaluations. The model inputs were well reported and commonly consisted of data from pivotal trials. Sensitivity analyses were conducted in the majority of studies and covered variables such as cost, effectiveness, hospitalization and treatment duration. Therapies (docetaxel, pemetrexed and erlotinib) are for the most part cost-effective/cost-saving second-line therapies compared with best supportive care (BSC). Six erlotinib HTAs, across NICE, SMC, and PBAC, and four pemetrexed HTAs, one by NICE and three by SMC, were identified. The CADTH website did not provide sufficient detail on the appraisals and was excluded. Certain aspects of the models and model assumptions, e.g. efficacy inputs, were criticized or determined unjustifiable by the NICE, SMC and PBAC appraisal committees. Erlotinib and pemetrexed were considered to be cost effective versus docetaxel by NICE and SMC in the final submissions. PBAC considered erlotinib to be cost effective versus BSC following a price reduction in 2008., Conclusion: Three-state Markov models are often used to conduct economic analysis in NSCLC and are regarded as appropriate to HTA agencies. Docetaxel, erlotinib and BSC are suitable comparators that should be considered for use in the model in the UK and Australia. Further, manufacturers should carefully select underlying assumptions used in the model, for both costs and clinical inputs, where the latter is derived from direct head-to-head trial data.

Objective: To develop a methodology for computing cost-effectiveness measures of a drug throughout its life cycle., Study Design: We developed a set of models that measure the long-term cost-effectiveness of 2 oncology drugs, paclitaxel and docetaxel, throughout their life cycles., Methods: The study combined pricing history of the drugs, US Food and Drug Administration approval dates, drug utilization from Medicare claims, and clinical effectiveness information from phase III studies reported in the scientific literature. These data were used to estimate the incremental cost-effectiveness ratio (ICER) at the time of market entry and by year thereafter. The study population included patients with cancer who were treated with paclitaxel or docetaxel., Results: The prices of paclitaxel and docetaxel dropped substantially due to patent expirations, while the number of users increased several fold because of subsequent empirical evidence and approval of new indications that resulted in greater efficacy. The ICER over a 10-year period was approximately 60% of the ICER at product launch for both drugs, and was further decreased when a longer-term perspective was taken., Conclusions: We demonstrated that the ICER of a drug can decrease substantially over its life cycle. Thus, cost-effectiveness at drug launch might be a poor indicator of the longterm value of the drug. The results of this study are based on the analysis of 2 prominent oncology drugs, paclitaxel and docetaxel. The results may not be generalizable to other drug classes or other oncology drugs for which new indications are less common.

Aim: To carry out a cost minimisation analysis including a comparison of the costs arising from first-line treatment by bevacizumab plus docetaxel (BD) versus bevacizumab plus paclitaxel (BP) of patients with metastatic breast cancer (mBC)., Patient and Methods: All consecutive patients with human epidermal growth receptor 2-negative mBC and treated at Besançon University hospital between 2006 and 2010 by a first-line therapy containing bevacizumab plus taxane were retrospectively studied. Economic analysis took into account costs related to drugs, hospitalization and healthcare travel., Results: Progression-free survival difference between the two treatments was insignificant (p-value=0.31). BP treatment was associated with a higher mean total cost than that of BD treatment, €53,093 ± 34,395 versus €60,196 ± 48,766, respectively., Conclusion: Whereas bevacizumab is recommended for first-line treatment of mBC with paclitaxel-based chemotherapy, our study has shown that BD treatment is the most cost-efficient regimen. It could be an attractive option in France, with a potential cost saving of €24,000,000 per year.

Objectives: The aim of this study was to evaluate the cost-utility of Docetaxel with doxorubicin and cyclophosphamide (TAC) and 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) in node-positive breast cancer patients in the south of Iran., Methods: A double blind study was done on a cohort of 100 patients suffering from breast cancer with node-positive over 8 months in the radiotherapy center of Namazi hospital, Shiraz-Iran. Health-related quality of life was assessed using questionnaire (QLQ-C30) from European Organization for Research and Treatment of Cancer (EORTC). QLQ-C30 scale scores were mapped to 15D and EuroQol 5D utilities to measure the quality-adjusted life-years (QALYs).Third party payer point of view was applied to measure and value the cost of treatments. Cost data were extracted from hospital and health insurance organizations. Robustness of the results was checked through a two way sensitivity analysis., Results: TAC was associated with higher deterioration in HRQoL during treatment and higher improvements over 4 months follow-up. On average, the cost of treatment per patient in TAC was 15 times higher than FAC (p < .001). In overall, TAC was resulted in lower QALYs and higher cost over study period., Conclusions: FAC was a dominant option versus TAC in short-term. The higher improvement in HRQoL over follow-up in TAC may not compensate the more intensive deterioration caused during treatment in short-term. The short time horizon of study may limit the generalizability of our findings and, hence, there is a need to conduct long-term economic evaluation studies whenever data is available to inform decision making.

Background: In a randomized controlled trial (RCT) of patients with recurrent, platinum-sensitive ovarian cancer, the combination weekly docetaxel and carboplatin was associated a with progression-free survival (PFS) of 13.7 months compared with 8.4 months for sequential, single-agent docetaxel followed by carboplatin. The objective of the current study was to construct a cost-utility model to compare these 2 regimens with the incorporation of prospectively collected quality-of-life (QoL) data., Methods: An RCT of concurrent docetaxel and carboplatin (cDC) versus docetaxel followed by carboplatin (sequential docetaxel and carboplatin [sDC]) was the basis for a Markov decision model, and the primary effectiveness outcome was PFS. Costs were estimated using US dollars based on Medicare reimbursements for chemotherapy regimens, bone marrow support, and management of adverse events. QoL data obtained using the Functional Assessment of Cancer Therapy-General questionnaire were converted to utilities. Costs and incremental cost-effectiveness ratios (ICERs) were reported in US dollars per quality-adjusted life year (QALY). Extensive 1-way sensitivity analyses and a Monte Carlo probabilistic sensitivity analysis were performed., Results: The least expensive strategy was sDC, which cost an average of $20,381, compared with cDC, which cost an average of $25,122. cDC had an ICER of $25,239 per QALY compared with sDC. cDC remained cost-effective, with an ICER <$50,000 per QALY, over a range of costs and estimates. In Monte Carlo sensitivity analysis using a $50,000 per QALY willingness-to-pay threshold, cDC was either dominant or cost-effective with an ICER <$50,000 per QALY in 83% of simulations., Conclusions: Combined weekly cDC appeared to be cost-effective compared with sDC as treatment strategy for patients with platinum-sensitive ovarian cancer, even when accounting for slightly lower QoL during treatment., (Copyright © 2011 American Cancer Society.)

Introduction: A comparison of clinical and economic outcomes among patients receiving second-line monotherapy with erlotinib, docetaxel, and pemetrexed for non-small cell lung cancer was conducted using a large network of outpatient community clinics., Methods: We identified 610 patients with advanced non-small cell lung cancer who received 2L treatment from July 1, 2006, to June 30, 2008, and were followed up through July 1, 2009, to evaluate progression-free survival (PFS), overall survival (OS), costs, and health resource utilization. Cox proportional hazards regression were used to compare PFS and OS across treatment cohorts. Economic outcomes were calculated per patient per month (PPPM) during a 12-month follow-up period., Results: There were 73 patients who received erlotinib, 87 received docetaxel, and 450 received pemetrexed. The median age was 67 years, and 55% were men. No significant differences in stage, baseline performance status, hemoglobin level, or body mass index were observed by treatment. The median OS was 132 days for docetaxel, 132 days for pemetrexed, and 155 days for erlotinib (p = 0.39). Adjusting for age, gender, stage, performance status, and hemoglobin level, there was no significant association between treatment type and OS (p = 0.36) or PFS (p = 0.26). Relative to pemetrexed, total adjusted costs PPPM was $1579 lower for docetaxel and $1584 lower for erlotinib (p < 0.05). Outpatient visits, laboratory procedures, and acute care visits were also less frequent with erlotinib relative to pemetrexed (-2.6 PPPM, p < 0.05)., Conclusions: We observed no significant differences in OS and PFS between patients receiving erlotinib, docetaxel, and pemetrexed. Nevertheless, erlotinib and docetaxel were associated with a statistically significant lower costs and resource use relative to pemetrexed.

Objective: Although the treatment of metastatic castrate-resistant prostate cancer (mCRPC) has improved with newer therapies, there is little understanding how these therapies have impacted resource use and associated expenditures; available estimates are dated. The current study examined contemporary healthcare utilization and associated costs for mCRPC patients and how these measures changed over time., Methods: This retrospective cohort analysis used medical and pharmaceutical insurance claims data from a large non-payer-owned integrated claims database of US commercial insurers. Amongst all patients with a prostate cancer diagnosis (n=256,464), those with ≥ 1 docetaxel claim (docetaxel cohort, n=3642) were identified as mCRPC patients. Within the docetaxel cohort, an additional 6-months follow-up cohort (n=2862) was identified, i.e., patients with at least 6 months of follow-up after the first docetaxel claim. Resource utilization and costs were identified for all-cause hospitalizations, emergency room (ER) visits, physician visits and ambulatory visits, and prostate cancer-related prescription treatments., Results: Significant increases in the mean per-patient-per-month (PPPM) count for the docetaxel cohort were observed for all medical resources measured (hospitalizations and ER, physician, and ambulatory visits) in the post-docetaxel period compared with the pre-docetaxel period (p<0.0001); similar significant increases were observed for the 6-months follow-up cohort in the last 6 months (prior to lost to follow-up date) compared with the period preceding the last 6 months (p<0.0408 ambulatory visits, p<0.0001 all other resources). Total docetaxel cohort costs (mean [standard deviation]) rose from an average PPPM cost of US$2593 (3208) in the pre-docetaxel period to US$5847 (6990) in the post-docetaxel period (p<0.0001); each of the individual resources measured (hospitalization, all healthcare visits, and prescription costs) demonstrated significant increases (p<0.0001)., Limitations: Retrospective study design., Conclusions: This large database analysis showed a significant increase in use of healthcare resources and associated costs among mCRPC patients following first-line docetaxel treatment.

Introduction: Erlotinib was recently approved in British Columbia (BC) as a second-line treatment for advanced NSCLC. A cost-effectiveness analysis was conducted which compares costs and effectiveness in patients who received second-line erlotinib with those in patients who received docetaxel., Methods: In a population of patients who have been treated with drugs (either erlotinib or docetaxel) for advanced NSCLC, overall survival (OS), progression-free survival (PFS), and probability of survival 1 year after beginning of second-line treatment (1YS) were determined using Kaplan-Meier and Cox proportional hazard analysis, as well as χ test. Costs were collected retrospectively from the perspective of the BC health care system., Results: Incremental mean OS was 1 day, and incremental mean cost was $2891. Neither costs nor effectiveness were statistically significantly different between groups. PFS and 1YS were also nonsignificantly different. Cox proportional hazard models were used to evaluate multivariate confounding., Conclusions: Erlotinib and docetaxel are statistically equivalent in terms of treatment cost and overall survival. As treatment practice patterns change, docetaxel may become more frequently prescribed. Therefore, the choice of whether to use erlotinib or docetaxel should be based on factors relating to patient preference rather than costs or effectiveness.

Background: The risk of recurrence following surgery in women with early breast cancer varies, depending upon prognostic factors. Adjuvant chemotherapy reduces this risk; however, increasingly effective regimens are associated with higher costs and toxicity profiles, making it likely that different regimens may be cost-effective for women with differing prognoses. To investigate this we performed a cost-effectiveness analysis of four treatment strategies: (1) no chemotherapy, (2) chemotherapy using cyclophosphamide, methotrexate, and fluorouracil (CMF) (a first generation regimen), (3) chemotherapy using Epirubicin-CMF (E-CMF) or fluorouracil, epirubicin, and cyclophosphamide (FEC60) (a second generation regimens), and (4) chemotherapy with FEC60 followed by docetaxel (FEC-D) (a third generation regimen). These adjuvant chemotherapy regimens were used in three large UK-led randomised controlled trials (RCTs)., Methods: A Markov model was used to simulate the natural progression of early breast cancer and the impact of chemotherapy on modifying this process. The probability of a first recurrent event within the model was estimated for women with different prognostic risk profiles using a parametric regression-based survival model incorporating established prognostic factors. Other probabilities, treatment effects, costs and quality of life weights were estimated primarily using data from the three UK-led RCTs, a meta-analysis of all relevant RCTs, and other published literature. The model predicted the lifetime costs, quality adjusted life years (QALYs) and cost-effectiveness of the four strategies for women with differing prognoses. Sensitivity analyses investigated the impact of uncertain parameters and model assumptions., Findings: For women with an average to high risk of recurrence (based upon prognostic factors and any other adjuvant therapies received), FEC-D appeared most cost-effective assuming a threshold of £20,000 per QALY for the National Health Service (NHS). For younger low risk women, E-CMF/FEC60 tended to be the optimal strategy and, for some older low risk women, the model suggested a policy of no chemotherapy was cost-effective. For no patient group was CMF chemotherapy the preferred option. Sensitivity analyses demonstrated cost-effectiveness results to be particularly sensitive to the treatment effect estimate for FEC-D and the future price of docetaxel., Interpretation: To our knowledge, this analysis is the first cost-effectiveness comparison of no chemotherapy, and first, second, and third generation adjuvant chemotherapy regimens for early breast cancer patients with differing prognoses. The results demonstrate the potential for different treatment strategies to be cost-effective for different types of patients. These findings may prove useful for policy makers attempting to formulate cost-effective treatment guidelines in the field of early breast cancer., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Within the past two years, three agents have garnered approval from the US FDA for the specific treatment of metastatic castration resistant prostate cancer (mCRPC) - (1) abiraterone, (2) cabazitaxel and (3) sipuleucel-T. In separate phase III studies, each agent led to an improvement in overall survival (OS) of 2-4 months over a suitable comparator. With these costly therapies all having potential application in the patient with mCRPC, multiple entities (industry, government, and the general public) must strategize to determine how the cost burden of these agents can be balanced with the potential gains for the individual patient. Herein, we provide a framework with which to approach this dilemma., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: The INTEREST (IRESSA NSCLC Trial Evaluating Response and Survival against Taxotere) trial compared gefitinib with docetaxel (Taxotere) in pretreated advanced non-small-cell lung cancer (NSCLC). Noninferiority for overall survival was concluded. Gefitinib had a better toxicity profile and greater improvements in quality of life (QoL). We undertook a cost-consequence analysis to estimate the direct medical costs of gefitinib compared with docetaxel., Patients and Methods: Summary data from INTEREST were used to derive resource utilization and direct costs from treatment start until drug discontinuation. Costs for treatment, adverse events, outpatient visits and investigations were calculated. Mean total cost-per-patient-per-arm was determined, and incremental cost was calculated. Utility values were generated from Functional Assessment of Cancer Therapy - Lung scores and compared between arms., Results: Incremental mean overall cost per patient for gefitinib over docetaxel was CAD $5161. Drug was the major contributor to overall cost in both arms. Longer mean duration of gefitinib therapy (134 versus 91 days) contributed to the incremental cost difference. The cost per 21-day cycle was similar in both arms ($1963 docetaxel, $2095 gefitinib)., Conclusion: The modest increase in cost associated with gefitinib supports its use as an alternative to docetaxel as second-line treatment of advanced NSCLC, particularly given the improvements in QoL, patient preference for oral therapy and better toxicity profile with gefitinib.

Although new chemotherapeutic drugs for metastatic breast cancer (MBC) have been approved over the past decade, it is unclear whether this has changed the overall outcome of patients. This study assessed the clinical and economic impacts of these drugs. We retrospectively studied MBC patients receiving chemotherapy in our institution over two time periods, 1994-1998 and 2003-2006. Patient characteristics and outcomes, and treatment characteristics and costs (€, 2008) were compared. Three hundred and one patients were identified, 149 patients in the first cohort and 152 in second one. The median number of lines of chemotherapy was similar in the two cohorts (three lines). The median costs of chemotherapy per patient nearly doubled over time, from 6,272 € in the 1994-1998 cohort to 13,035 € in the 2003-2006 cohort (P < 0.001). No survival difference was observed between the two groups, with a 3-year survival rate estimated to 41% in the 1994-1998 cohort and 44% in the 2003-2006 cohort (P = 0.52). In multivariate analysis, prognostic factors associated with longer overall survival were single metastatic site (HR 0.48; P < 10⁻³), bone metastases (HR = 0.67; P = 0.007) and positive hormone receptors (HR 0.56; P = 0.0002). New chemotherapeutic agents induced a significant cost increase over time. The limited size and heterogeneity of our cohort do not allow any conclusion concerning their impact on survival.

Objectives: In Mexico, breast cancer is the second leading cause of cancer mortality among females. For patients with advanced breast cancer (ABC) resistant to anthracyclines and taxanes (AT), there are limited treatment options. There is a scarcity of data regarding clinical management of this population and treatment costs at this stage of the disease. The objective of this study was to describe the treatment patterns of care for metastatic breast cancer after AT and the associated cost from the point-of-view of the Mexican Public Health Care Sector., Methods: Between January 1, 2004 and December 31, 2007, a retrospective cohort of adult female ABC patients resistant to AT was developed by reviewing and extracting key data from medical charts. We conducted a retrospective, transversal and descriptive analysis of the patient data. Target population data files were obtained from 414 patients from 3 public hospitals in México., Results: Capecitabine, vinorelbine and cyclophosphamide were the most commonly prescribed agents, however clinical drug therapy management of the disease was different within and among the three hospitals included in the study. This difference translated into a disparity of prescription costs, ranging from an average of $122.22 pesos/patient/month (cyclophosphamide, IC 95% $94.43-$150.01) to $37,835.53 pesos/patient/month (capecitabine+trastuzumab IC 95% $34,953.18-$40,717.88) for the first treatment after AT., Conclusions: The results highlight a lack of standardized care for patients and suggest that differences in treatment patterns are not only a reflection of scarcity of scientific data and diversity of prescription preferences among physicians but also of economic restrictions. Ultimately, there is a clear unmet medical need to be addressed through evidence-based medicine alternatives that support efficacy and cost effectiveness treatments., (Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

This paper presents a summary of the evidence review group (ERG) report into the use of bevacizumab (Avastin®, Roche) in combination with a taxane for the treatment of untreated metastatic breast cancer (mBC). The main clinical effectiveness data were derived from a single, open-label randomised controlled trial (RCT) (E2100) that evaluated the addition of bevacizumab to weekly (q.w.) paclitaxel in patients with human epidermal growth factor receptor 2-negative mBC who had not previously received chemotherapy for advanced disease. This trial reported statistically significant increases in median progression-free survival (PFS) for the addition of bevacizumab (5.8-11.3 months). Median overall survival was not significantly different between the two groups; whether this is a true null finding or due to crossover between treatment arms cannot be established, as relevant data were not collected. The manufacturer reported that the addition of bevacizumab to paclitaxel q.w. therapy was associated with a significant improvement in quality of life, as measured by FACT-B (functional assessment of cancer therapy for breast cancer) scores. However, the ERG noted that these results were based on extreme imputed values, the removal of which led to non-significant differences in quality of life. The manufacturer conducted an indirect comparison. However, owing to methodological limitations and concerns about the validity and exchangeability of the included trials, the ERG did not consider the findings to be reliable. One additional relevant RCT [AVADO (Avastin and Docetaxel); BO17708] evaluating the addition of bevacizumab to docetaxel was excluded from the manufacturer's submission. This was summarised by the ERG. In terms of response rate and PFS, AVADO reported a markedly smaller benefit of adding bevacizumab to docetaxel than that reported for adding bevacizumab to q.w. paclitaxel in E2100. AVADO also reported no statistically significant effect of combination therapy versus docetaxel in terms of overall survival. The manufacturer developed a de novo economic model that considered patients with the same baseline characteristics as women in the E2100 trial. The model assessed BEV + PAC - bevacizumab 10 mg/kg every 2 weeks in combination with paclitaxel 90 mg/m2 weekly for 3 weeks followed by 1 week of rest; PAC q.w. - paclitaxel (monotherapy) 90 mg/m2 weekly for 3 weeks followed by 1 week of rest; DOC - docetaxel (monotherapy) 75 mg/m2 on day 1 every 21 days (considered current UK NHS clinical practice in the submission); and GEM + PAC - gemcitabine 1250 mg/m2 on days 1 and 8 plus paclitaxel 175 mg/m2 on day 1 every 21 days. Pairwise comparisons were made between BEV + PAC and PAC (using the E2100 trial), BEV + PAC and DOC, and BEV + PAC and GEM + PAC. Based on NHS list prices, the manufacturer's model estimated incremental cost-effectiveness ratios (ICERs) for BEV + PAC of £ 117,803, £ 115,059 and £ 105,777 per QALY gained, relative to PAC, DOC and GEM + PAC regimens, respectively. If the NHS Purchasing and Supply Agency prices for PAC with a 10-g cap on the cost per patient of BEV were used instead, the ICERs for BEV + PAC were estimated at £ 77,314, £ 57,753 and £ 60,101 per QALY, respectively. The submission suggested that the regimen of BEV + DOC is not cost-effective because it is considered less effective and more costly than BEV + PAC. Analysis by the ERG suggested that alternative assumptions can increase the ICERs further and, based on current prices, no plausible changes to the model assumptions will bring the ICERs for BEV + PAC lower.