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5554 ispor

  1. 1. Cost-Effectiveness of Ribociclib plus Letrozole for Treatment-Naïve Post-Menopausal Women with HR+/HER2- Advanced or Metastatic Breast Cancer from a US Third-Party Payer Perspective Suri G,1 Mistry R,1 Young KC,2 Hettle R,1 May JR,1 Brixner D,3 Oderda G,3 Biskupiak J,3 Tang D,4 Bhattacharyya D,5 * Bhattacharyya S,5 Mishra D,5 Dalal A4 1 PAREXEL, London, UK; 2 PAREXEL, Horsham, PA, USA; 3 University of Utah, Salt Lake City, UT, USA; 4 Novartis, East Hanover, NJ, USA; 5 Novartis, Hyderabad, Telangana, India *Corresponding author (devarshi.bhattacharyya@novartis.com) Background • Treatment options for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or meta-static breast cancer in post-menopausal patients include aromatase inhibitors (e.g., letrozole), selective estrogen receptor modulators (e.g., tamoxifen), estrogen receptor antagonists (e.g., fulvestrant), and, most recently, oral, highly-selective, cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors1,2 • Clinicalstudieshaveshownthatthecombinationofribocicliborpalbociclibwith letrozoleisatolerable,safe,andefficaciousalternativetoletrozolemonotherapyfor first-linepostmenopausalHR+/HER2-advancedbreastcancer3-5 Objective • To evaluate the cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole or versus letrozole monotherapy in the first-line treatment of post- menopausal women with HR+/HER2- advanced or metastatic breast cancer from a United States (US) private third-party payer perspective Methods Model Overview • A partitioned survival model was developed in Microsoft Excel® 2010 with a three-state structure comprising progression free (PF; either with objective response or with stable disease), progressed disease (PD), and death (Figure 1) Figure 1. Health State Structure of the Economic Model Progression free (response/stable disease) Progressed disease Death • The analysis was performed using two primary sources for modelling progression-free survival (PFS; MONALEESA-25 ) and overall survival (OS; PALOMA-13 ) • Costs and benefits were calculated over a 40-year lifetime horizon with a 1-month cycle length and half-cycle correction • The model incorporated subsequent (second- and third-line) therapies for patients who progressed while on treatment; the subsequent use of a CDK4/6 inhibitor was considered clinically inappropriate Clinical Inputs • State occupancies over time were estimated from PFS and OS curves –– For letrozole monotherapy, using a Weibull parametric model, PFS was estimated from the control arm of MONALEESA-2 (PFS and objective response)5 and OS from the control arm of PALOMA-1 (OS)3 –– For ribociclib plus letrozole, using the same model, PFS was estimated from the active arm of MONALEESA-2 (PFS and objective response)5 and OS from the active arm of PALOMA-1 (OS)3 –– For palbociclib plus letrozole, survival was modelled using objective response, PFS, and OS for letrozole adjusted for the relative efficacy of palbociclib plus letrozole versus letrozole from a meta-analysis of PALOMA-1 and PALOMA-26 • Objectiveresponsetotherapywasassumedtoaccruelinearlyoverthefirst12months (inlinewithMONALEESA-2),5 afterwhichitwasassumedtodeclinewithPFS • Treatment duration for letrozole was modelled on the time spent in the PF health state. Treatment duration with a CDK4/6 inhibitor was modelled independently of PFS, using data from MONALEESA-25 . Discontinuation for palbociclib was modelled from the ribociclib data adjusted for any differences in PFS between CDK 4/6 inhibitors (hazard ratio [HR]=1.010; 95% CI: 0.730-1.390) • The comparative efficacy of CDK 4/6 inhibitors was obtained from a Bayesian network meta-analysis7 Cost and Utility Data Cost Data • All costs were in 2016 US dollars inflated using the Consumer Price Index (CPI)8 • Only costs relating to direct reimbursable medical care were considered; these included drug acquisition, administration, and monitoring, disease management (health state costs), subsequent treatments, and adverse events • DrugacquisitioncostsweresourcedfromMedi-SpanPriceRx®9 usingthelowest wholesaleacquisitioncost(WAC)ofeachmedicationandallowedforpatientco- payments(ribociclibplusletrozoleorpalbociclibplusletrozole,$567;letrozole,$11); thetreatmentacquisitioncostofribociclibwasprovidedbyNovartis(Table1) • Monthly treatment administration costs were taken from the 2016 Physician’s Fee Schedule using Medicare facility prices.10 No administration costs were applied to oral formulations • Drug-specific monitoring costs were applied to ribociclib and palbociclib at treatment initiation and at fixed intervals up to a maximum of 6 or 12 months, respectively, as directed by the product labels (Table 1)11,12 • Costs of subsequent (second- or third-line) treatment were applied as a one-off cost at the start of the model evaluation. Market share and treatment data were sourced from Novartis (data on file), and the lowest WAC formulation on the market was used9 . Eribulin was used as a proxy representing all chemotherapies because it was the highest cost first-line chemotherapy • The model included serious adverse events (AEs) (Common Terminology Criteria for Adverse Events Grade ≥3) reported more frequently with ribociclib5 or palbociclib3 versus placebo (anemia, diarrhea, fatigue, infection, nausea, febrile neutropenia, pulmonary embolism, and vomiting) and that (from previous HTA submissions and consultations with modelling experts) were deemed relevant and related to treatment, were likely to result in hospitalization, or had a meaningful impact on patient well-being • The probability of patients experiencing a Grade ≥3 AE was obtained from clinical studies (Table 1).3-5 The cost of each AE was assumed to reflect an average hospitalization related to that event8,13,14 and was applied as a one-off cost at the beginning of the model Utility Data • Life-years (LYs) were calculated from survival projections whereas quality- adjusted life-years (QALYs) were calculated from time spent in each state combined with health state utility (HSU) values • Utility values were obtained from the literature and relevant clinical trials (Novartis, data on file)15-17 Table 1. Model Inputs Rib + Let Let monotherapy Pal + Let Drugs and disease management Drug acquisition costs ($) 600 mg: 10,950 400 mg: 8,760 200 mg: 4,380 0a 10,963 Drugmonitoringcosts($) Initial: 138 Follow-up: 22 0 Initial: 42 Follow-up: 11 Disease management costs ($) PF: 687 PD: 6,200 PF: 687 PD: 6,200 PF: 687 PD: 6,200 Adverse event (≥Grade 3) Incidence (%) Unit cost ($) Diarrhea 1.2 0.9 1.7 7,377 Fatigue 2.4 0.9 2.3 6,908 Infection 4.2 2.4 4.4 10,128 Nausea 2.4 0.6 0.6 6,182 Febrile neutropenia 1.2 0.0 0.4 21,156 Pulmonary embolism 0 0.3 5.0 10,036 Vomiting 3.6 0.9 0.4 5,246 Anemia 1.2 1.2 5.5 6,777 Utility inputsb Complete/partial response 0.837 (0.007) Stable disease 0.830 (0.006) Progressed disease 0.443 (0.044) a WAC price of $8; however, with a co-payment of $11, the acquisition costs is reduced to $0. b Mean (standard error); Rib, Ribociclib; Let, Letrozole; Pal, Palbociclib Analyses • The outputs of the analysis included total and incremental costs and QALYs gained with ribociclib plus letrozole versus palbociclib plus letrozole and versus letrozole monotherapy) • Costs and outcomes were discounted at 3.0% per annum18 • A one-way deterministic sensitivity analysis (DSA) was performed by varying key parameters: discount rate (0%–6% variation), treatment acquisition costs (±10%) for ribociclib plus letrozole and the selected comparator, health state (PF, PD) costs (±10%), AE incidence rates (±10%), and utilities for PF and PD health states (±10%) • Probabilistic uncertainty was assessed through a Monte Carlo probabilistic sensitivity analysis (PSA; n=1000 iterations) of clinical data (survival distributions for PFS and OS and time to treatment distribution), cost data (drug acquisition and monitoring costs, disease management costs, and AE costs), and utility data (utility weights assigned to PF and PD states, and disutility of AEs) Results Base Case Deterministic Base Case Results • Treatment with ribociclib plus letrozole cost of $432,095 versus $475,132 for palbociclib plus letrozole and $287,180 for letrozole monotherapy (Table 2) • The total QALYs for ribociclib plus letrozole were 3.07 (PFS=2.17; PD=0.90) versus 2.99 (PF=1.99; PD=1.00) for palbociclib plus letrozole and 2.38 (PF=1.26; PD=1.12) for letrozole monotherapy (Table 2) Table 2. Total and Incremental Costs and QALYs Treatment Incremental Rib + Let Let Pal + Let Rib + Let vs. Let Rib + Let vs. Pal + Let Drug costs ($) CDK-4/6 inhibitor 228,605 0 256,393 228,605 -27,788 Letrozole 0 0 0 0 0 Monitoring 196 0 116 196 80 Health-state costs ($) PF 21,790 12,834 19,931 8,956 1,859 Responder 9,672 3,830 7,104 5,842 2,567 Stable disease 12,118 9,003 12,826 3,115 -708 PD 150,772 187,606 167,575 -36,834 16,803 Second-line+ 27,285 84,027 27,285 -56,742 0 AEs 1,349 573 1,735 776 -386 End of life 2,098 2,140 2,098 -42 0 Total ($) 203,294 287,180 218,623 -83,886 -15,330 Total cost ($) 432,095 287,180 475,132 144,915 -43,037 Total QALY 3.07 2.38 2.99 0.689 0.086 PF 2.17 1.26 1.99 PD 0.90 1.12 1.00 ICER 210,369 Dominated byRib+Let AE, Adverse event; CDK 4/6, Cyclin-dependent kinase 4 and 6; ICER, Incremental cost-effectiveness ratio; Let, Letrozole; Pal, Palbociclib; PD, Progressed disease; PF, Progression free; Rib, Ribociclib; QALY, Quality-adjusted life year • Ribociclib plus letrozole provided a cost reduction of $43,037 and a gain of 0.086 QALYs compared with palbociclib plus letrozole and was therefore dominant versus palbociclib plus letrozole • Compared with letrozole monotherapy, ribociclib plus letrozole was associated with an incremental cost of $144,915 and an incremental QALY gain of 0.689, giving an ICER of $210,369 per QALY Sensitivity Analyses • From the DSA, the key model drivers were the PFS HR for palbociclib plus letrozole versus letrozole, the OS HRs for ribociclib plus letrozole, PD health state costs, the utility of objective response, and the cost discount rate (Figure 2) Figure 2. Key Model Drivers from Deterministic Sensitivity Analysis 190,000 195,000 200,000 205,000 210,000 215,000 220,000 225,000 230,000 Inc. rate forneutropenia Inc. rate for infection Utility (PD) Health state costs (PF) Health state costs (PD) Utility (stable disease) HR OS (vs. letrozole) Discountrate -costs Utility (response) Discountrate -benefits ICER ($) 21,698 31,698 41,698 51,698 61,698 71,698 Inc. rate for infection Health state costs (PF) Utility (stable disease) Discount rate - benefits Discount rate - costs Utility (response) Health state costs (PD) HR PFS of palbociclib (vs. letrozole) HR OS (vs. letrozole) HR OS of palbociclib (vs. letrozole) Netmonetarybenefit($) HR, Hazard ratio; Inc., Including; OS: Overall survival; PD, Progressed disease; PF, Progression free; PFS: Progression-free survival; vs., Versus • From the PSA, ribociclib plus letrozole remained dominant versus palbociclib plus letrozole, with a mean incremental cost reduction of $45,511 and a mean increase of 0.040 QALYs (Figure 3) Figure 3. Cost-effectiveness Acceptability Curve for Ribociclib Plus Letrozole Versus Palbociclib Plus Letrozole 0 10 20 30 40 50 60 70 80 90 100 0 50000 100000 150000 200000 Percentage Threshold($'s) Ribociclib + Letrozole Palbociclib + Letrozole • In comparison with letrozole, ribociclib plus letrozole resulted in a mean incremental cost of $143,834 and a mean incremental QALY of 0.757 equating to an ICER of $190,001 per QALY gained. The probability that ribociclib plus letrozole was cost-effective versus letrozole at thresholds of $50,000, $100,000 and $200,000 per QALY gained was 1.60, 6.30 and 50.50%, respectively Conclusions • The results from this analysis suggest that, in the US, ribociclib plus letrozole is a cost-effective alternative to palbociclib plus letrozole for the first-line treatment of post-menopausal women with HR+/HER2- advanced or metastatic breast cancer • Furthermore, at willingness-to-pay thresholds above $198,000 per QALY, treatment with ribociclib plus letrozole is also cost-effective versus letrozole monotherapy • The conclusions of this analysis are broadly consistent with other published analyses of the cost-effectiveness of CDK4/6 inhibitors in HR+/HER2- breast cancer19,20 References 1. Cardoso, F. Ann Oncol. 2017; 28:16-33. 2. Gradishar, W.J. J Natl Compr Canc Netw. 2016; 14:324-54. 3. Finn, R.S. Lancet Oncol. 2015; 16:25-35. 4. Finn, R.S. J Clin Oncol. 2016; 34:507. 5. Hortobagyi, G.N. N Engl J Med. 2016; 375:1738-48. 6. Analysis Group. NMA of Treatments in HR+ HER2- Advanced Breast Bancer in Postmenopausal Women. 2016. 7. Analysis Group. Systematic Literature Review and Network Meta-Analysis of Clinical Trials in the First-line Setting for Advanced HR+ HER2- Breast Cancer. 2017. 8. U.S. Bureau of Labor Statistics. 2016. 9. Medispan Price Rx. [cited 2017; Available from: https://pricerx.medispan.com/IngredientName. aspx. 10. Medicare. Medicare Facility Prices 2016. 11. Novartis. KISQALI Prescribing Information. 2017. 12. Pfizer Inc. IBRANCE Prescribing Information. 2017. 13. Healthcare Cost and Utilization Project (National Inpatient Sample. 2013. 14. Michels, S.L. Pharmacoeconomics. 2012; 30:809- 23. 15. Devlin, N.J. Health Econ, 2017; doi 10.1002/hec.3584. 16. Lloyd, A. Br J Cancer. 2006; 95:683-90. 17. Hudgens, S. Value Health. 2014; 17:A557. 18. Gold, M.R. Cost-Effectiveness in Health and Medicine. 1996. 19. Bhattacharya, K. Value Health. 2016; 19:A150. 20. Matter-Walstra, K. Breast Cancer Res Treat. 2017; 163:635. Presented at the ISPOR 20th Annual European Congress, 4-8 November, Glasgow, UK. This study was funded by Novartis. PCN133 Text: Q01f13 To: 8NOVA (86682) US Only +18324604729North,CentralandSouthAmericas;Caribbean;China +447860024038 UK,Europe & Russia +46737494608 Sweden, Europe Visit the webat: http://novartis.medicalcongressposters.com/Default.aspx?doc=01f13 Scan this QR code Copies of this poster obtained through Quick Response (QR) Code are for personal use only and may not be reproduced without permission from the author of this poster.

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