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Cost-effectiveness analysis of 1st through 3rd line sequential targeted therapy in HER2-positive metastatic breast cancer in the United States.

ABSTRACT: Based on available phase III trial data, we performed a cost-effectiveness analysis of different treatment strategies that can be used in patients with newly diagnosed HER2-positive metastatic breast cancer (mBC).We constructed a Markov model to assess the cost-effectiveness of four different HER2 targeted treatment sequences in patients with HER2-positive mBC treated in the U.S. The model followed patients weekly over their remaining life expectancies. Health states considered were progression-free survival (PFS) 1st to 3rd lines, and death. Transitional probabilities were based on published phase III trials. Cost data (2015 US dollars) were captured from the U.S. Centers for Medicare and Medicaid Services (CMS) drug payment table and physician fee schedule. Health utility data were extracted from published studies. The outcomes considered were PFS, OS, costs, QALYs, the incremental cost per QALY gained ratio, and the net monetary benefit. Deterministic and probabilistic sensitivity analyses assessed the uncertainty around key model parameters and their joint impact on the base-case results.The combination of trastuzumab, pertuzumab, and docetaxel (THP) as first-line therapy, trastuzumab emtansine (T-DM1) as second-line therapy, and lapatinib/capecitabine third-line resulted in 1.81 QALYs, at a cost of $335,231.35. The combination of trastuzumab/docetaxel as first line without subsequent T-DM1 or pertuzumab yielded 1.41 QALYs, at a cost of $175,240.69. The least clinically effective sequence (1.27 QALYs), but most cost-effective at a total cost of $149,250.19, was trastuzumab/docetaxel as first-line therapy, T-DM1 as second-line therapy, and trastuzumab/lapatinib as third-line therapy.Our results suggest that THP as first-line therapy, followed by T-DM1 as second-line therapy, would require at least a 50 % reduction in the total drug acquisition cost for it to be considered a cost-effective strategy.

SUBMITTER: Diaby V

PROVIDER: S-EPMC5329168 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Cost-effectiveness analysis of 1st through 3rd line sequential targeted therapy in HER2-positive metastatic breast cancer in the United States.

Diaby Vakaramoko V Adunlin Georges G Ali Askal A AA Zeichner Simon B SB de Lima Lopes Gilberto G Kohn Christine G CG Montero Alberto J AJ

Breast cancer research and treatment 20160921 1

<h4>Purpose</h4>Based on available phase III trial data, we performed a cost-effectiveness analysis of different treatment strategies that can be used in patients with newly diagnosed HER2-positive metastatic breast cancer (mBC).<h4>Patients and methods</h4>We constructed a Markov model to assess the cost-effectiveness of four different HER2 targeted treatment sequences in patients with HER2-positive mBC treated in the U.S. The model followed patients weekly over their remaining life expectancie ...[more]

PMID: 27654970

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Project description:The approval of new immunotherapies has dramatically changed the treatment landscape of metastatic melanoma. These survival gains come with trade-offs in side effects and costs, as well as important considerations for third-party payer systems, physicians, and patients.To develop a Markov model to determine the cost-effectiveness of nivolumab, ipilimumab, and nivolumab-ipilimumab combination as firstline therapy in metastatic melanoma, while accounting for differential effectiveness in programmed death-ligand 1 (PD-L1) positive and negative patients.A 3-state Markov model (PD-L1 positive stable disease, PD-L1 negative stable disease, and progression and/or death) was developed using a U.S. societal perspective with a lifetime time horizon of 14.5 years. Transition probabilities were calculated from progression-free (PF) survival data reported in the CheckMate-067 trial. Costs were expressed in 2015 U.S. dollars and were determined using national sources. Adverse event (AE) management was determined using immune-related AE (irAE) data from CheckMate-067, irAE management guides for nivolumab and ipilimumab, and treatment guidelines. Utilities were obtained from published literature, using melanoma-specific studies when available, and were weighted based on incidence and duration of irAEs. Base case, one-way sensitivity, and probabilistic sensitivity analyses were conducted.Nivolumab-ipilimumab combination therapy was not the cost-effective choice ($454,092 per PF quality-adjusted life-year [QALY]) compared with nivolumab monotherapy in a base case analysis at a willingness-to-pay threshold of $100,000 per PFQALY. Combination therapy and nivolumab monotherapy were cost-effective choices compared with ipilimumab monotherapy. PD-L1 positive status, utility of nivolumab and combination therapy, and medication costs contributed the most uncertainty to the model. In a population of 100% PD-L1 negative patients, nivolumab was still the optimal treatment, but combination therapy had an improved incremental cost-effectiveness ratio (ICER) of $295,903 per PFQALY. Combination therapy became dominated by nivolumab, when 68% of the sample was PD-L1 positive. In addition, the cost of ipilimumab would have to decrease to < $21,555 per dose for combination therapy to have an ICER < $100,000 per PFQALY and to < $19,151 (a 42% reduction) to be more cost-effective than nivolumab monotherapy.Nivolumab-ipilimumab combination therapy was not cost-effective compared with nivolumab monotherapy, which was the most cost-effective option. Professionals in managed care settings should consider the pharmacoeconomic implications of these new immunotherapies as they make value-based formulary decisions, and future cost-effectiveness studies are completed.No funding supported this study. Merino was a contractor with EMD Serono at the time of this study but does not have any conflicts of interest and did not receive any funding related to this study. All other authors have no financial disclosures and no conflicts of interest. All the authors contributed to the study concept and design. Tran, McDowell, and Barcelon took the lead in data collection, along with Oh, Keyvani, and Merino. All authors except Merino contributed to data interpretation. The manuscript was written by Oh, Tran, McDowell, and Wilson and revised by Oh, Tran, McDowell, Wilson, and Keyvani. This analysis was presented at Academy of Managed Care Pharmacy Managed Care & Specialty Pharmacy Annual Meeting 2016, April 19-22, 2016, in San Francisco, California, and at the International Society for Pharmacoeconomics and Outcomes Research Annual International Meeting, May 21-25, 2016, in Washington DC.

Project description:The cost-effectiveness of first-line treatment with lapatinib plus letrozole for postmenopausal women with hormone receptor-positive (hr+), human epidermal growth factor receptor 2-positive (her2+) metastatic breast cancer (mbc) has not been assessed from the Canadian health care system and societal perspectives.A partitioned survival analysis model with 3 health states (alive, pre-progression; alive, post-progression; dead) was developed to estimate direct and indirect costs and quality-adjusted life years (qalys) with lapatinib-letrozole, letrozole, anastrozole, or trastuzumab-anastrozole as first-line treatment. Clinical inputs for lapatinib-letrozole and letrozole were taken from the EGF30008 trial (NCT00073528). Clinical inputs for anastrozole and trastuzumab-anastrozole were taken from a network meta-analysis of published studies. Drug costs were obtained from the manufacturer's price list, the Quebec list of medications, and imsBrogan. Other costs were taken from the Ontario Health Insurance Plan's Schedule of Benefits and Fees and published studies. A 10-year time horizon was used. Costs and qalys were discounted at 5% annually. Deterministic and probabilistic sensitivity analyses were performed to assess the effects of changes in model parameters.Quality-adjusted life years gained with lapatinib-letrozole were 0.236 compared with trastuzumab-anastrozole, 0.440 compared with letrozole, and 0.568 compared with anastrozole. Assuming a health care system perspective, incremental costs were $5,805, $67,029, and $67,472 respectively. Given a cost per qaly threshold of $100,000, the probability that lapatinib-letrozole is preferred was 21% compared with letrozole, 36% compared with anastrozole, and 68% compared with trastuzumab-anastrozole. Results from the societal perspective were similar.In postmenopausal women with hr+/her2+ mbc receiving first-line treatment, lapatinib-letrozole may not be cost-effective compared with letrozole or anastrozole, but may be cost-effective compared with trastuzumab-anastrozole.

Project description:BackgroundInformation and knowledge about cost of illness and labour productivity in patients with HER2-positive early-stage and metastatic breast cancer treated with trastuzumab is limited. The aim of this study was to estimate the direct and indirect costs associated with treatment of HER2-positive breast cancer among patients with early-stage and metastatic breast cancer, treated with trastuzumab, in a 10-year period after diagnosis.Materials and methodsThis study included all Danish HER2-positive breast cancer patients (≥ 18 years) treated with trastuzumab between 2005 and 2016 identified in The Danish Patient Register and the Danish Cancer Register. Furthermore, we identified patients experiencing metastatic or recurrent breast cancer. For the study populations, we estimated total direct costs and indirect costs for one year prior to the breast cancer diagnosis and up to 10 years after diagnosis compared with a group of matched controls free of breast cancer. In addition to The Danish Patient Register and Cancer Register, we applied patient level data from The Civil Registration System, The National Pathology Register, National Health Service Register for Primary Care, Register of Medicinal Product Statistics, Register of Municipal Services, The DREAM database, and Population's Education Register.ResultsWe identified 4,153 HER2-positive breast cancer patients, whereof 27% were identified with metastatic or recurrent breast cancer. During the follow-up period of 10 years, we estimated excess direct costs of EUR 115,000 among the total study population compared to controls; EUR 211,000 among patients with metastases or recurrence; and EUR 89,000 among patients without metastases or recurrence. Direct costs were found to be highest in the first year after diagnosis and also peaked in the year after recurrence. Labour productivity was significantly lower among patients with recurrence 10 years after breast cancer diagnosis compared with controls.ConclusionsIn this study, we estimated the direct and indirect cost associated with HER2-positive breast cancer. The costs were significantly higher during the 10 years after diagnosis compared to the control group, specifically among patients experiencing metastases or recurrence of breast cancer.

Project description:ImportanceImmune checkpoint inhibitor combination therapy has recently become the standard of care for first-line treatment of metastatic nonsquamous non-small cell lung cancer. The implications of these first-line treatments are considerable, given the potential population of patients eligible to receive them and their high cost.ObjectiveTo evaluate the cost-effectiveness of adding atezolizumab to bevacizumab, carboplatin, and paclitaxel as a first-line treatment strategy for patients with metastatic nonsquamous non-small cell lung cancer in the United States.Design, setting, and participantsIn this economic evaluation, a primary microsimulation model was developed to assess atezolizumab combination vs bevacizumab, carboplatin, and paclitaxel alone in the first line (base case 1). A secondary model was developed to assess these treatments along with pembrolizumab combination and platinum doublet chemotherapy (base case 2). Treatment strategies and other simulated conditions were based on those from the IMpower150 and KEYNOTE-189 clinical trials. The study perspective was the US health care sector. One million patients with metastatic nonsquamous non-small cell lung cancer were simulated for each treatment group. This study was performed from February 2019 through May 2019.Main outcomes and measuresIncremental cost-effectiveness ratios were compared with a willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY).ResultsIn base case 1, in which 1 million patients were simulated, treating with bevacizumab, carboplatin, and paclitaxel in the first line was associated with a mean cost of $112 551 (95% CI, $112 450-$112 653) and a mean survival of 1.48 QALYs (95% CI, 1.47-1.48 QALYs) per patient. Atezolizumab plus bevacizumab, carboplatin, and paclitaxel was associated with a mean cost of $244 166 (95% CI, $243 864-$244 468) and a mean survival of 2.13 QALYs (95% CI, 2.12-2.13 QALYs) per patient, for an estimated incremental cost-effectiveness ratio of $201 676 per QALY (95% CI, $198 105-$205 355 per QALY). In base case 2, in which 1 million patients were simulated, pembrolizumab combination therapy was associated with a mean cost of $226 282 (95% CI, $226 007-$226 557) and a mean survival of 2.45 QALYs (95% CI, 2.44-2.46 QALYs) per patient. Pembrolizumab combination dominated atezolizumab plus bevacizumab, carboplatin, and paclitaxel, leading to an incremental cost-effectiveness ratio of $116 698 per QALY (95% CI, $115 088-$118 342 per QALY) between pembrolizumab combination and bevacizumab, carboplatin, and paclitaxel. Atezolizumab combination was not cost-effective at a willingness-to-pay threshold of $100 000 per QALY.Conclusions and relevanceIn this simulated model economic analysis, atezolizumab combination was not cost-effective compared with bevacizumab, carboplatin, and paclitaxel and provided suboptimal incremental benefit compared with cost vs pembrolizumab combination for first-line treatment. Although atezolizumab combination therapy provides clinical benefits, price reductions may be necessary for this treatment strategy to become cost-effective.

Project description:BackgroundSurvival of patients with human epidermal growth receptor 2 (HER2)-positive metastatic breast cancer (MBC) has improved dramatically since trastuzumab has become available, although the disease eventually progresses in most patients. This study investigates the outcome (overall survival [OS] and time to next treatment [TNT]) in MBC patients pretreated with trastuzumab in the adjuvant setting (TP-group) compared with trastuzumab-naïve patients (TN-group) in order to investigate the possibility of trastuzumab resistance.Patients and methodsPatients treated with first-line HER2-targeted-containing chemotherapy were eligible for the study. A power analysis was performed to estimate the minimum size of the TP-group. OS and TNT were estimated using Kaplan-Meier curves and multivariable Cox proportional hazards models.ResultsBetween January 1, 2000, and June 1, 2014, 469 patients were included, of whom 82 were in the TP-group and 387 were in the TN-group. Median OS and TNT were significantly worse in the TP-group compared with the TN-group (17 vs. 30 months, adjusted hazard ratio [HR] 1.84 [1.15-2.96], p = .01 and 7 vs. 13 months, adjusted HR 1.65 [1.06-2.58], p = .03) after adjustment for age, year of diagnosis, disease-free interval, hormone receptor status, metastatic site, and cytotoxic regimens.ConclusionFirst-line trastuzumab-containing treatment regimens are less effective in patients with failure of adjuvant trastuzumab compared with trastuzumab-naïve patients and might be due to trastuzumab resistance. The impact of trastuzumab resistance on the response on dual HER2 blockade with trastuzumab and pertuzumab and how resistance mechanisms can be used in the optimization of HER2-targeted treatment lines need further investigation.Implications for practiceEvidence on the efficacy of palliative trastuzumab-based therapy after failure of trastuzumab in the adjuvant setting is limited because of a minority of patients treated with adjuvant trastuzumab in clinical trials. In this study, less clinical benefit of palliative trastuzumab-based therapy was observed in patients relapsing after adjuvant trastuzumab compared with no adjuvant trastuzumab treatment. Subgroup analyses and multivariable analyses revealed that this was independent of possible confounding factors, including adjuvant taxane-treatment. This might suggest a clinically meaningful impaired efficacy of trastuzumab after previous, in this case adjuvant, trastuzumab therapy. These results could have implications for treatment decision-making after short progression-free intervals on trastuzumab-containing regimens in the palliative setting.

Dataset Information

Cost-effectiveness analysis of 1st through 3rd line sequential targeted therapy in HER2-positive metastatic breast cancer in the United States.

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Cost-effectiveness analysis of 1st through 3rd line sequential targeted therapy in HER2-positive metastatic breast cancer in the United States.

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