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Supplementary Figure 1 Kaplan-Meier curve fittingAbbreviations: PFS, progression-free survival; OS, overall survival.Supplementary Table 1 Patient baseline demographic and clinical characteristicsCharacteristicsRibociclib + Fulvestrant(n = 484), No. (%)Placebo + Fulvestrant(n = 242), No. (%)Median age, years (range)63 (31-89)63 (34-86)ECOG performance status0311 (64.3)158 (65.3)1172 (35.5)83 (34.3)missing1 (0.2)1 (0.4)Disease stage at study entry II2 (0.4)0 (0.0) III4 (0.8)2 (0.8) IV478 (98.8)239 (98.8)missing0 (0.0)1 (0.4)Hormone receptor status ER positive481 (99.4)241 (99.6) PR positive353 (72.9)167 (69.0)Metastatic site, No. (%) Visceral293 (60.5)146 (60.3) Bone only102 (21.1)51 (21.1) Lymph nodes199 (41.1)115 (47.5)No. of sites of metastasis<3308 (63.6)147 (60.7)≥3176 (36.4)94 (38.8)missing0 (0.0)1 (0.4)Prior endocrine therapy status Treatment naive238（49.2）129（53.3） Up to one line236 (48.8)109 (45)Notes: The baseline demographic and clinical characteristics of the hypothetical patients in the model were derived from the relevant data of MONALEESA-3 trial.10,13 Supplementary Table 2 Drug doses and unit price DrugDoseUnit price ($)Cost for one cycle ($/4 weeks)ReferenceProgression free diseaseRibociclib600 mg/day orally on days 1-21 of a 28-day cycle219.61/200mg13,835.4310,23Fulvestrant500 mg on day 1 of each 28-day cycle, with an additional dose on day 15 of cycle 156.46/25mg1,129.2 10,22First progressionPyrimidine analoguesCapecitabine1000-1250 mg/m2×1.79m2 twice daily days 1-14; every 3 weeks.2.458/500mg412.94410,22,24Gemcitabine800-1200 mg/m2 ×1.79m2 days 1, 8, and 15; every 28 days3.864/200mg103.74810,22,25Taxanes Paclitaxel175 mg/m2×1.79m2 day 1; every 21 days (or 80 mg/m2 day 1 weekly)0.129/mg73.89110,22,26,27 Nab-Paclitaxel100 mg/m2 or 125 mg/m2 days 1, 8, and 15; every 28 days12.718/mg6,829.56610,22,28Platinum compoundsCarboplatinArea under the concentration-time curve of 6 mg/ml/min×70ml/min day 1; every 21 days2.79/50mg31.2510,22,29 Cisplatin75 mg/m2 day 1; every 21 days.1.914/10mg25.69510,22,30Anthracyclines Doxorubicin60-75 mg/m2 day 1; every 21 days (or 20 mg/m2 day 1 weekly) 2.998/10mg42.93110,22,31,32 Liposomal doxorubicin50 mg/m2 day 1; every 28 days.82.35/2mg3,685.16310,23,33Aromatase inhibitors Exemestane25 mg once daily each 28-day cycle9.44/25mg264.324,10,23 Letrozole2.5 mg once daily each 28-day cycle3.39/2.5mg94.929,10,23,34 Anastrozole1 mg once daily each 28-day cycle2.84/mg79.529,10,23,35Anti-estrogensFulvestrant500 mg day1 every 14 days for the first three injections and then every 28 days56.46/25mg1129.210,22Tamoxifen20 mg once daily each 28-day cycle0.323/10mg18.0889,10,23Targeted therapy Bevacizumab10 mg/kg days 1 and 15; every 28 days.79.555/10mg1,113.7710,23,36Supplementary Table 3 Results for subgroup analysesSample sizeOS HR (95% CI)ICERProbability ofCost-Effectiveness at WTP of$150,000/QALYSubgroupsRibociclibPlaceboAge<65 yr2581290.76 (0.54-1.07)601,0120.10%≥65 yr2261130.70 (0.49-1.00)564,5820.20%PgR status Positive3531670.74 (0.55-1.00)588,3970.30%Negative113690.72 (0.45-1.15)576,2630.20%Hormone-receptor statusER-positive and PgR-positive3501670.73 (0.54- 0.98)582,2710Other134740.74 (0.48-1.13)588,3970.30%Liver or lung involvementYes2421220.81 (0.58-1.12)634,8490.20%No2421190.65 (0.45-0.93)537,2120.50%Bone lesion onlyYes102510.60 (0.33-1.07)512,1900.10%No3821900.76 (0.58-1.00)601,0120.20%No. of sites of metastasis<33081470.75 (0.54-1.04)545,0720.10%≥3176420.73 (0.50-1.05)594,6430.40%Treatment line First line2371280.70 (0.48-1.02)582,2710.10%Early relapse or second line2371090.73 (0.53-1.00)564,5820.20%Degree of response to prior endocrine therapyEndocrine na?ve139740.64 (0.38 - 1.05)582,2710.10%Endocrine sensitive2891400.74 (0.55 - 1.01)588,3970.20%Endocrine resistant53250.70 (0.37 - 1.33)564,5820.30%Abbreviations: ICER, incremental cost-effectiveness ratio; HR, hazard ratio; OS, overall survival; QALY, quality-adjusted life year; WTP, willingness-to-pay.Supplementary Table 4 CHEERS checklistSection/item Item NoRecommendationReported?Title and abstractTitle1Identify the study as an economic evaluation or use more specific terms such as “cost-effectiveness analysis”, and describe the interventions compared.YesAbstract2Provide a structured summary of objectives, perspective, setting, methods (including study design and inputs), results (including base case and uncertainty analyses), and conclusions.YesIntroductionBackground and objectives3Provide an explicit statement of the broader context for the study. Present the study question and its relevance for health policy or practice decisions. YesMethodsTarget population and subgroups4Describe characteristics of the base case population and subgroups analyzed, including why they were chosen. YesSetting and location 5State relevant aspects of the system(s) in which the decision(s) need(s) to be madeYesStudy perspective6Describe the perspective of the study and relate this to the costs being evaluated.YesComparators7Describe the interventions or strategies being compared and state why they were chosen.YesTime horizon8State the time horizon(s) over which costs and consequences are being evaluated and say why appropriate.YesDiscount rate9Report the choice of discount rate(s) used for costs and outcomes and say why appropriate.YesChoice of health outcomes10Describe what outcomes were used as the measure(s) of benefit in the evaluation and their relevance for the type of analysis performed.YesMeasurement of effectiveness11aSingle study-based estimates: Describe fully the design features of the single effectiveness study and why the single study was a sufficient source of clinical effectiveness data.Yes11bSynthesis-based estimates: Describe fully the methods used for identification of included studies and synthesis of clinical effectiveness data. N/AMeasurement and valuation of preference based outcomes12If applicable, describe the population and methods used to elicit preferences for outcomes.N/AEstimating resources and costs13aSingle study-based economic evaluation: Describe approaches used to estimate resource use associated with the alternative interventions. Describe primary or secondary research methods for valuing each resource item in terms of its unit cost. Describe any adjustments made to approximate to opportunity costs.N/A13bModel-based economic evaluation: Describe approaches and data sources used to estimate resource use associated with model health states. Describe primary or secondary research methods for valuing each resource item in terms of its unit cost. Describe any adjustments made to approximate to opportunity costs.YesCurrency, price date, and conversion14Report the dates of the estimated resource quantities and unit costs. Describe methods for adjusting estimated unit costs to the year of reported costs if necessary. Describe methods for converting costs into a common currency base and the exchange rate.YesChoice of model15Describe and give reasons for the specific type of decision-analytical model used. Providing a figure to show model structure is strongly recommended.Yes Assumptions16Describe all structural or other assumptions underpinning the decision-analytical model. Yes Analytical methods17Describe all analytical methods supporting the evaluation. This could include methods for dealing with skewed, missing, or censored data; extrapolation methods; Yes methods for pooling data; approaches to validate or make adjustments (such as half cycle corrections) to a model; and methods for handling population heterogeneity and uncertainty.Yes ResultsStudy parameters18Report the values, ranges, references, and, if used, probability distributions for all parameters. Report reasons or sources for distributions used to represent uncertainty where appropriate. Providing a table to show the input values is strongly recommended.Yes Incremental costs and outcomes19For each intervention, report mean values for the main categories of estimated costs and outcomes of interest, as well as mean differences between the comparator groups. If applicable, report incremental cost-effectiveness ratios.YesCharacterizing uncertainty20aSingle study-based economic evaluation: Describe the effects of sampling uncertainty for the estimated incremental cost and incremental effectiveness parameters, together with the impact of methodological assumptions (such as discount rate, study perspective).N/A20bModel-based economic evaluation: Describe the effects on the results of uncertainty for all input parameters, and uncertainty related to the structure of the model and assumptions. YesCharacterizing heterogeneity21If applicable, report differences in costs, outcomes, or cost-effectiveness that can be explained by variations between subgroups of patients with different baseline characteristics or other observed variability in effects that are not reducible by more information.N/ADiscussionStudy findings, limitations, generalizability, and current knowledge22Summarize key study findings and describe how they support the conclusions reached. Discuss limitations and the generalizability of the findings and how the findings fit with current knowledge.YesOtherSource of funding23Describe how the study was funded and the role of the funder in the identification, design, conduct, and reporting of the analysis. Describe other non-monetary sources of support.YesConflicts of interest24Describe any potential for conflict of interest of study contributors in accordance with journal policy. In the absence of a journal policy, we recommend authors comply with International Committee of Medical Journal Editors recommendations.YesSupplementary References4.Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012;366(6):520-529. 9.Im SA, Lu YS, Bardia A, et al. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med. 2019;381(4):307-316. 10.Slamon DJ, Neven P, Chia S, et al. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. N Engl J Med. 2020;382(6):514-524. 13.Slamon DJ, Neven P, Chia S, et al. Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3. J Clin Oncol. 2018;36(24):2465-2472. 22.Centers for Medicare and Medicaid Services: Medicare Part B Drug Average Sale Price. 2020; . Accessed 16 May, 2020. 23. [online] 2020; https ://drugs .com/price-guide /faslodex. Accessed 13 May 2020.24.Bajetta E, Procopio G, Celio L, et al. Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women. J Clin Oncol. 2005;23(10):2155-2161.25.Seidman AD. Gemcitabine as single-agent therapy in the management of advanced breast cancer. Oncology (Williston Park). 2001;15(2 Suppl 3):11-14. 26.Seidman AD, Tiersten A, Hudis C, et al. Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol. 1995;13(10):2575-2581.27.Perez EA, Vogel CL, Irwin DH, Kirshner JJ, Patel R. Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2001;19(22):4216-4223. 28.Gradishar WJ, Krasnojon D, Cheporov S, et al. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2009;27(22):3611-3619. 29.Isakoff SJ, Mayer EL, He L, et al. TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With Biomarker Assessment in Metastatic Triple-Negative Breast Cancer. J Clin Oncol. 2015;33(17):1902-1909. 30.Silver DP, Richardson AL, Eklund AC, et al. Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. J Clin Oncol. 2010;28(7):1145-1153. 31.Chan S, Friedrichs K, Noel D, et al. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol. 1999;17(8):2341-2354. 32.Gasparini G, Dal Fior S, Panizzoni GA, Favretto S, Pozza F. Weekly epirubicin versus doxorubicin as second line therapy in advanced breast cancer. A randomized clinical trial. Am J Clin Oncol. 1991;14(1):38-44.33.O'Brien ME, Wigler N, Inbar M, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004;15(3):440-449. 34.Finn RS, Martin M, Rugo HS, et al. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med. 2016;375(20):1925-1936. 35.Mehta RS, Barlow WE, Albain KS, et al. Combination anastrozole and fulvestrant in metastatic breast cancer. N Engl J Med. 2012;367(5):435-444.36.Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357(26):2666-2676. ................
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