Cost-effectiveness comparison of dalpiciclib and

abemaciclib Combined with an aromatase inhibitor

as first-line treatment for HR+/ HER2− advanced
breast cancer
Juan Hong
National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen
Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Tujia Chen
Boai Hospital of Zhongshan
Jun Meng
National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen
Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Zhengzheng Xia (  xiazhengzheng@cicams-sz.org.cn )
National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen
Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Research Article

Keywords: HR+/HER2 − advanced breast cancer, Dalpiciclib, Abemaciclib, Cost-effectiveness, Aromatase

inhibitor

Posted Date: October 23rd, 2023

DOI: https://doi.org/10.21203/rs.3.rs-3468411/v1

License:   This work is licensed under a Creative Commons Attribution 4.0 International License.
Read Full License

Additional Declarations: No competing interests reported.

Page 1/17
Abstract
Background
Dalpiciclib and abemaciclib, both CDK4/6 inhibitors, have been approved by the China National Medical
Products Administration for the first-line treatment of postmenopausal women with hormone receptor-
positive (HR+) and human epidermal growth factor receptor-2 negative (HER2−) advanced breast cancer
(ABC). As the first domestically developed CDK4/6 inhibitor in China, there has been no previous
economic evaluation of dalpiciclib. This study aimed to assess the cost-effectiveness of dalpiciclib
compared to abemaciclib when used in combination with letrozole for the first-line treatment of
HR+/HER2 − ABC from the perspective of healthcare payers in China.

Methods
A Markov model with three health states was constructed to evaluate the health and economic outcomes
of first-line treatment with dalpiciclib plus letrozole and abemaciclib plus letrozole for HR+/HER2 − ABC.
The efficacy data was obtained from the MONARCH3 and DAWNA-2 trials, while utility data was derived
from published reports. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios
(ICERs) were calculated. Sensitivity analyses were performed to explore variations in the model results.

Results
Compared to abemaciclib plus letrozole, dalpiciclib plus letrozole resulted in 5.13 additional QALYs, with
an ICER of $27,305/QALY. At a willingness-to-pay (WTP) threshold of the gross domestic product (GDP)
per capita in China for 2022 ($38,223/QALY), the probability of dalpiciclib plus letrozole being cost-
effective was 75%. Sensitivity analysis results were consistent with those of the base-case analysis.

Conclusions
From the perspective of Chinese healthcare payers, the combination of dalpiciclib and letrozole appears
to be a more cost-effective strategy when compared to abemaciclib plus letrozole for the first-line
treatment of patients with HR+/HER2 − ABC in China.

Introduction
Global Cancer Statistics for 2020 presented that female breast cancer was the most commonly
diagnosed cancer and the fifth leading cause of cancer-related deaths worldwide [1]. In China, breast
cancer accounted for 16.72% of all new cancer cases, and breast cancer-related deaths accounted for
9.9% of all female cancer deaths [2]. The majority of breast cancer patients were initially diagnosed with
localized disease (94–97%), and 3–6% had new metastatic disease at diagnosis. Additionally, 10–30% of
Page 2/17
early-stage breast cancer patients later developed systemic recurrence [3]. Approximately 70% of patients
with metastatic breast cancer have the HR+/HER2 − subtype [4]. Unfortunately, advanced breast cancer
(ABC) has a poor prognosis, with a 5-year survival rate of only 26% for distant HR+/HER2 − breast cancer
[5]. Since ABC remains incurable, treatment goals should encompass not only improving survival but also
maintaining the quality of life and palliation of symptoms [6, 7].

The main treatment for postmenopausal women with HR+/HER2 − ABC has been single-agent endocrine
therapy, typically with aromatase inhibitors (AIs) such as letrozole or anastrozole. However, resistance
eventually occurs [8]. Several studies have demonstrated that adding a cyclin-dependent kinase 4/6
(CDK4/6) inhibitor to letrozole/anastrozole significantly enhances efficacy. Consequently, the
combination of endocrine therapy and a CDK4/6 inhibitor has become the preferred first-line treatment
for HR+/HER2 − ABC in most parts of the world [9–11]. Abemaciclib and dalpiciclib, both CDK4/6
inhibitors, were approved for first-line use in combination with AI for patients with HR+/HER2 − ABC by the
Chinese National Medical Products Administration (NMPA) in 2020 and 2023, respectively. This approach
is also recommended by the Chinese Society of Clinical Oncology (CSCO) Diagnosis and Treatment of
Breast Cancer Guideline as the first-line treatment for HR+/HER2 − ABC [12].

The clinical efficacy of abemaciclib in combination with a nonsteroidal AI (anastrozole or letrozole) was
evaluated in the MONARCH 3 (NCT02246621) study [13–15]. MONARCH 3 was a randomized, phase III,
double-blind study involving postmenopausal women with HR+/HER2 − locoregionally recurrent breast
cancer who had not received prior systemic therapy. A total of 493 patients were assigned to receive
either abemaciclib (150 mg twice daily continuously) (n = 328) or placebo (once daily) (n = 165), both in
combination with 1 mg anastrozole or 2.5 mg letrozole daily. The primary objective was progression-free
survival (PFS). The results of the study showed that the abemaciclib arm achieved a significantly longer
median PFS compared to the placebo arm (28.18 months versus 14.76 months; hazard ratio, 0.54).

Efficacy data for dalpiciclib plus letrozole or anastrozole was derived from the DAWNA-2 (NCT03966898)
study [16]. DAWNA-2 was a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial
conducted in 42 hospitals in China. It assessed the efficacy and safety of dalpiciclib plus letrozole or
anastrozole as first-line therapy for patients with HR+/HER2 − ABC who had not received prior systemic
therapy in the advanced setting. A total of 456 patients were eligible and randomly assigned to either the
dalpiciclib group (150 mg per day for 3 weeks, followed by 1 week off in a 4-week cycle) (n = 303) or the
placebo group (once daily for 3 weeks, followed by 1 week off in a 4-week cycle) (n = 153). Both groups
also received endocrine therapy with either 2.5 mg letrozole or 1 mg anastrozole orally once daily
continuously. The primary endpoint was PFS, and results showed that the dalpiciclib group had a
significantly longer median PFS compared to the placebo group (30.6 months versus 18.2 months;
hazard ratio, 0.51). Serious adverse events were reported in 36 (12%) patients in the dalpiciclib group and
10 (7%) patients in the placebo group.

As the first domestically developed CDK4/6 inhibitor in China, there has been no previous economic
evaluation of dalpiciclib. Therefore, the objective of this study was to assess the cost-effectiveness of

Page 3/17
dalpiciclib compared to abemaciclib when combined with AI for the first-line treatment of HR+/HER2 −
ABC in China.

Methods
Model overview
This study adhered to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS)
reporting guidelines [17, 18]. We developed a Markov model to simulate the costs and health benefits
associated with the treatment of HR+/HER2- ABC with abemaciclib and dalpiciclib plus letrozole/
anastrozole. The model incorporated three discrete health states that represented different stages of the
disease: progression-free (PF), progressed disease (PD), and death (Fig. 1). Since the treatment schedule
for dalpiciclib was 21 days followed by 7 days off, the cycle length in the Markov model was set to one
month. The lifetime horizon was 15-years because the 5-year survival rate was 26% and the initial health
status for all patients was progression-free survival [19, 20]. All patients entered the model in the PF state
and remained in this state until disease progression or death. Patients in the PD state could either remain
in this state or die.

The outcomes of this model included life years (LYs), quality-adjusted life years, and costs. According to
Chinese guidelines for pharmacoeconomic evaluations, costs and QALYs were discounted at an annual
rate of 5%. Incremental cost-effectiveness ratios (ICERs) were calculated, representing the cost per
additional QALY gained. The cost-effectiveness threshold in China was set at $38,223 (3 times the per
capita gross domestic product of China in 2022) [21, 22].

Clinical efficacy
Survival parameters were mainly obtained from the Kaplan–Meier (KM) curve of the MONARCH 3 and
DAWNA-2 trials[13–16]. As patients in DAWNA-2 trials are followed for a limited period of time, with most
patients not reaching the endpoint event by the trial's conclusion, we simulated overall survival (OS)
curves to account for incomplete data. These OS curves predicted the median survival benefit of first-line
treatment with CDK4/6 inhibitors plus aromatase inhibitors.

We utilized the Engauge Digitizer software to extract digitized data points from the PFS and OS Kaplan–
Meier curves of the MONARCH 3 and DAWNA-2 trials. Individual patient data were reconstructed using
standard statistical analyses as described by Guyot, et al [23]. The following parametric survival
functions were considered: the exponential distribution, the Weibull distribution, and the log-logistic
distribution. The best-fitted distribution was chosen for the model based on the Akaike Information
Criterion (AIC) and Bayesian Information Criterion (BIC), selecting the distribution with the smallest AIC or
BIC value [24].
Cost estimates
Page 4/17
This analysis adopted the perspective of healthcare payers in China, which considered only direct
medical costs. These costs included first- and second-line treatment, management of treatment-related
serious adverse events, disease management costs (including outpatient visits, hospitalizations,
laboratory scans, and tests), and terminal care. Drug costs were estimated based on patient dosing
schedules and unit costs, with costs calculated per cycle. Unit drug costs were obtained from the
Shenzhen pharmaceutical trading platform [25]. Costs related to subsequent treatment, adverse event
management, and end-of-life care were sourced from published literature [26–31]. Regarding subsequent
treatment, we assumed that patients taking oral abemaciclib plus letrozole or anastrozole and dalpiciclib
plus letrozole or anastrozole would receive the same subsequent treatment after progression of advanced
breast cancer [15]. For adverse event management costs, only events of grade ≥ 3 in the MONARCH 3
and DAWNA-2 trials were included [14, 16]. All costs were adjusted to US dollars in 2022. Chinese Yuan
was converted to US dollars by using the exchange rate formula: 1 US $ = 6.7261 CNY [32]. Key costs are
shown in Table 1.

Page 5/17
 Table 1
Model parameters of clinical data,costs and utilities: baseline values, ranges, and distributions.
Parameters inputs Baseline Distribution Reference
Value(Range)

Survival model for Dalpiciclib plus letrozole

PFS* AIC = 584.05, BIC = Log-logistic Estimated

592.79

OS* AIC = 226.17, BIC = Weibull Estimated

234.22

Survival model for Abemaciclib plus

letrozole

PFS* AIC = 495.64, BIC = Exponential Estimated

501.00

OS* AIC = 226.17, BIC = Weibull Estimated

534.22

Direct costs

PFS on Dalpiciclib plus letrozole 3079 (2463–3079) Gamma [25, 26–

31]

PD on Dalpiciclib plus letrozole 3863 (3091–4636) Gamma [25, 26–

31]

PFS on Abemaciclib plus letrozole 1179 (943–1179) Gamma [26–31]

PD on Abemaciclib plus letrozole 2088 (1671–2506) Gamma [26–31]

Management of SAEs * in Dalpiciclib plus 958 (766–1149) Gamma [17, 26–

letrozole 31]

Management of SAEs* on Abemaciclib plus 358 (286–429) Gamma [16, 26–

letrozole 31]

subsequent treatment 910 (728–1092) Gamma [15, 25]

Disease management Of PFS 614 (492–737) Gamma [26–31]

Disease management Of PD 1199 (959–1439) Gamma [26–31]

End-of-life 2155 (1724–2858) Gamma [26–31]

Utility values of Dalpiciclib plus letrozole

PFS* state 0.79 (0-0.79) Beta [36]

PD* state 0.45 (0-0.45) Beta [36]

*PFS Progression-free survival, OS Overall survival, SAEs Severe adverse events, PD Progressed
disease
Page 6/17
 Parameters inputs Baseline Distribution Reference
Value(Range)

Utility values of Abemaciclib plus letrozole

PFS* state 0.65 (0-0.65) Beta [35]

PD* state 0.56 (0-0.56) Beta [35]

Discount rate 0.05 (0–0.08) Beta [22]

*PFS Progression-free survival, OS Overall survival, SAEs Severe adverse events, PD Progressed
disease

Utility estimates
Quality-adjusted life years (QALYs) were estimated using health state utility (HSU) values, and separate
HSU values were estimated for patients in the PF and PD states.The HSU values for different health
states were derived from patient-reported outcomes from the full MONARCH 3 population [18], utilizing
the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire
Core 30 (QLQ-C30) and Breast Cancer Questionnaire (BR23) to measure the health-related quality of life
[33, 34]. The HSU values used in the model are summarized in Table 1.

Sensitivity analysis
In the base-case analysis, ICERs were presented as cost-effectiveness outcome measure and calculated
as the incremental cost per additional LY. In accordance with Chinese guidelines for pharmacoeconomic
evaluations, we adopted 3 times the per capita gross domestic product (GDP) of China in 2022 as the
WTP threshold, equating to $38,223 per QALY [21, 22].

One-way deterministic and probabilistic sensitivity analyses were performed to assess the uncertainty of
the results. In the one-way deterministic sensitivity analyses (DSA), key model input parameters were
adjusted one-by-one to their respective low and high values, as detailed in Tables 1. The ranges for the
parameters were determined based on credible intervals or by assuming a variance of 20% from the base-
case values. The results of the one-way sensitivity analyses are presented in a Tornado diagram. For the
probabilistic sensitivity analyses (PSA), parameters were sampled using the Monte Carlo method,
generating 1000 replicated outcomes. Results were presented on a cost-effectiveness plane and cost-
effectiveness acceptability curve. Each parameter was put into the model with diferent distribution types:
Gamma distributions for costs related to disease management, drug acquisition, monitoring, and adverse
events, and Beta distributions for the utility weights assigned to PF and PD states [37].

Results
Base-case analysis

Page 7/17
The results of the deterministic analysis are presented in Table 2. In the HR+/HER2 − ABC patients, when
compared to abemaciclib plus letrozole, dalpiciclib plus letrozole yielded an additional 5.13 QALYs (44.43
QALYs vs. 39.3 QALYs), corresponding to an incremental cost of $140000. The ICER was calculated to be
$27305/QALY gained, which was lower than the WTP of three times the GDP per capita in China.

Table 2
Summary of results of the base-case analysis.
Regimens Costs ($) QALYs* Incremental Incremental ICER*
Cost ($) QALYs*

Dalpiciclib plus 437502.1206 44.4297 140000.1756 5.1273 27304.5694

letrozole

Abemaciclib plus 297501.9450 39.3023 NA NA NA

letrozole

* QALYs: Quality-adjusted life years, ICER:Incremental cost-efectiveness ratio

Sensitivity analysis

The one-way deterministic sensitivity analyses suggested that the results of the model were more
sensitive to the utility of PD and PFS for dalpiciclib plus letrozole group and abemaciclib plus letrozole
group(Fig. 2). For PSA, the cost-effectiveness plane illustrated the results of 1,000 Monte Carlo iterations
(Fig. 3). Comparing dalpiciclib plus letrozole with abemaciclib plus letrozole, the cost-effectiveness
acceptability curve indicated a nearly 75% probability of cost-effectiveness at the WTP threshold of
$38,223/QALY, consistent with the base-case analysis result (Fig. 4).

Discussion
In this study, we constructed a Markov model to assess the cost-effectiveness of dalpiciclib plus letrozole
versus abemaciclib plus letrozole as the first-line treatment for HR+/HER2 − ABC patients in China from
the perspective of the Chinese healthcare system. Our results indicated that the therapy of dalpiciclib plus
letrozole produced an additional 5.13 life years and 44.43 QALYs compared to abemaciclib plus letrozole.
The calculated ICER was $27,305/QALY gained, which was below the WTP threshold of three times GDP
per capita in China. this finding indicated that dalpiciclib plus letrozole strategy was a cost-effective
option. The probabilistic sensitivity analysis also demonstrated robustness of this result, and the
conclusion was further strengthened by the deterministic sensitivity analysis.

For an indirect comparison between the abemaciclib plus letrozole and dalpiciclib plus letrozole
treatments, it's essential to ensure comparable baselines between the groups. According to the baseline
characteristics of patients reported in the MONARCH 3 study and DAWNA-2 study, the proportion of
Disease-free interval (De novo metastatic,41% vs. 41%), Visceral metastases at study entry (61% vs. 55%)
in the two groups were similar. Nonetheless, certain disparities were observed, such as the proportion of
prior endocrine therapy, median age, Post-menopausal status, and the inclusion of letrozole as an

Page 8/17
endocrine therapy partner [13–16]. The DAWNA-2 study, conducted in China, provided insights into the
local epidemiological nuances of advanced breast cancer. Compared to western counterparts, Chinese
patients tend to be younger and exhibit a lower frequency of prior endocrine therapy and Post-
menopausal status, indicative of a more favorable prognosis.

With China increasingly emphasizing economic evaluation evidence in medical insurance coverage
negotiations, executing cost-effectiveness analyses for innovative medications to furnish a holistic
decision-making foundation has become paramount. Zeng N et al. showed that, in comparison with
Palbociclib plus AI and ribociclib plus AI, only abemaciclib plus AI proved cost-effective at a WTP of
$38,029/QALY from the Chinese payers' perspective [38]. however, the economic evidence of dalpiciclib
plus AI versus abemaciclib plus AI in China is currently lacking. To our knowledge, this is the first analysis
attempting to evaluate the economic outcomes of these treatment regimens for HR+/HER2 − ABC
patients.

This study has several limitations that should be mentioned. (1) Lack of local utility data for HR+/HER2 −
ABC patients from the DAWNA-2 study, Consequently, the accuracy of the model will require updating
when such data become available in China. (2) The OS curve in the DAWNA-2 study was not yet fully
mature, leading to the utilization of parameter distribution fitting for simulation. While this approach
enhances result accuracy, it's important to recognize that it introduces an element of estimation. (3) As
there were some inconsistencies in the baseline characteristics, the heterogeneity of baseline
characteristics cannot be well balanced, which might increase the bias of the results. It is crucial to note
that this analysis is based on updated data published in 2023. We will revisit and update our results once
the final data are accessible for analysis.

Conclusions
This study demonstrated that dalpiciclib plus letrozole is potentially more cost-effective option than
abemaciclib plus letrozole for the first-line treatment of HR+/HER2- ABC from the perspective of the
Chinese healthcare system at a WTP threshold of $38223/QALY. This finding could guide clinicians and
health policymakers towards more informed decisions for the management of HR+/HER2- ABC.

Abbreivations
HR + Hormone receptor-positive

HER2 − Human epidermal growth factor receptor-2 negative

ABC Advanced breast cancer

QALYs Quality-adjusted life-years

ICER Incremental cost-effectiveness ratio

Page 9/17
CDK4/6 Cyclin-dependent kinase 4/6

NMPA National Medical Products Administration

CSCO Chinese Society of Clinical Oncology

AIs Aromatase inhibitors

PFS Progression-free survival

HR Hazard ratio

CHEERS Consolidated Health Economic Evaluation Reporting Standards

PF Progression-free

PD Progressed disease

LYs Life years

KM Kaplan– Meier

OS Overall survival

AIC Akaike Information Criterion

BIC Bayesian Information Criterion

HSU Health state utility

EORTC European Organization for Research and Treatment of Cancer

QLQ-C30 Quality of Life Questionnaire Core 30

BR23 Breast Cancer Questionnaire

GDP Gross domestic product

WTP Willingness-to-pay

DSA Deterministic sensitivity analyses

PSA Probabilistic sensitivity analys

Declarations
Acknowledgments

Not applicable.
Page 10/17
Author contributions

X.Z.Z and M.J conceived and designed the study protocol. C.T.J and X.Z.Z retrieved and collected the
data, C.T.J ,X.Z.Z and H.J conducted the statistical analysis and interpretation of the
results. H.J and X.Z.Z completed the drafting of the article, and revised the manuscript. All authors read
and approved the final manuscript.

Funding

This work is supported by Shenzhen High-level Hospital Construction Fund, Guangdong Pharmaceutical
Association Comprehensive Drug Evaluation fund (Grant no. 2022-1115-29), and Shenzhen
Pharmaceutical Association Hospital Pharmacy Research Fund (Grant no. sz2022A28), and China
Medical Education Association Research Fund (Grant no. 2023WSJSPGZXKT-12).

The sponsors had no roles in the study process.

Availability of data and material

Datasets are available through the corresponding author upon reasonable request.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no conflict of interest.

Author details

1
Department of pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer
Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College,
Shenzhen, China. 2Department of Pharmacy, Boai Hospital of Zhongshan, Zhongshan, China

References
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics
2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.
CA Cancer J Clin. 2021; 71:209-49. https://doi.org/10.3322/caac.21660.

Page 11/17
 2. Zheng R, Zhang S, Zeng H, Wang S, Sun K, Chen R, et al. Cancer incidence and mortality in China,
2016. J Natl Cancer Cent. 2022; 2:1-9. https://doi.org/10.1016/j.jncc.2022.02.002.
3. Daily K, Douglas E, Romitti PA, Thomas A. Epidemiology of De Novo Metastatic Breast Cancer. Clin
Breast Cancer. 2021; 21:302-08. https://doi.org/10.1016/j.clbc.2021.01.017.
4. Howlader N, Altekruse SF, Li CI, Chen VW, Clarke CA, Ries LAG, et al. US Incidence of Breast Cancer
Subtypes Defined by Joint Hormone Receptor and HER2 Status. J Natl Cancer Inst. 2014;
106:dju055. https://doi.org/10.1093/jnci/dju055.
5. Jiang S, Meng Q, Ji F, Yin Y, Liu X, Shi W, et al. A bibliometric analysis of metastatic breast cancer:
two-decade report (2002-2022). Front Oncol. 2023; 13:1229222.
https://doi.org/10.3389/fonc.2023.1229222.
6. Cardoso F, Paluch-Shimon S, Senkus E, Curigliano G, Aapro MS, André F, et al. 5th ESO-ESMO
international consensus guidelines for advanced breast cancer (ABC). Annals of Oncology. 2020;
31:1623-49. https://doi.org/10.1016/j.annonc.2020.09.010.
7. Gombos A, Goncalves A, Curigliano G, Bartsch R, Kyte JA, Ignatiadis M, et al. How I treat endocrine-
dependent metastatic breast cancer. ESMO Open. 2023; 8:100882.
https://doi.org/10.1016/j.esmoop.2023.100882.
8. Caswell-Jin JL, Plevritis SK, Tian L, Cadham CJ, Xu C, Stout NK, et al. Change in Survival in
Metastatic Breast Cancer with Treatment Advances: Meta-Analysis and Systematic Review. JNCI
Cancer Spectr. 2018; 2:pky062. https://doi.org/10.1093/jncics/pky062.
9. Burstein HJ, Somerfield MR, Barton DL, Dorris A, Fallowfield LJ, Jain D, et al. Endocrine Treatment
and Targeted Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-
Negative Metastatic Breast Cancer: ASCO Guideline Update. J Clin Oncol. 2021; 39:3959-77.
https://doi.org/10.1200/jco.21.01392.
10. Elfgen C, Bjelic-Radisic V. Targeted Therapy in HR+ HER2− Metastatic Breast Cancer: Current Clinical
Trials and Their Implications for CDK4/6 Inhibitor Therapy and beyond Treatment Options. Cancers.
2021; 13:5994. https://doi.org/10.3390/cancers13235994.
11. Huppert LA, Gumusay O, Idossa D, Rugo HS. Systemic therapy for hormone receptor‐positive/human
epidermal growth factor receptor 2‐negative early stage and metastatic breast cancer. CA Cancer J
Clin. 2023; 73:480-515. https://doi.org/10.3322/caac.21777.
12. CSCO. Guidelines of Chinese Society Of Clinical Oncology (CSCO). Diagnosis and Treatment of
Breast Cancer Guideline 2023. People’s Medical Publishing House Press. 2023.
13. Goetz MP, Toi M, Campone M, Sohn J, Paluch-Shimon S, Huober J, et al. MONARCH 3: Abemaciclib
As Initial Therapy for Advanced Breast Cancer. J Clin Oncol. 2017; 35:3638-46.
https://doi.org/10.1200/jco.2017.75.6155.
14. Johnston S, Martin M, Di Leo A, Im S-A, Awada A, Forrester T, et al. MONARCH 3 final PFS: a
randomized study of abemaciclib as initial therapy for advanced breast cancer. NPJ Breast Cancer.
2019; 5:5. https://doi.org/10.1038/s41523-018-0097-z.

Page 12/17
15. Johnston S, O’Shaughnessy J, Martin M, Huober J, Toi M, Sohn J, et al. Abemaciclib as initial therapy
for advanced breast cancer: MONARCH 3 updated results in prognostic subgroups. NPJ Breast
Cancer. 2021; 7:80. https://doi.org/10.1038/s41523-021-00289-7.
16. Zhang P, Zhang Q, Tong Z, Sun T, Li W, Ouyang Q, et al. Dalpiciclib plus letrozole or anastrozole
versus placebo plus letrozole or anastrozole as first-line treatment in patients with hormone receptor-
positive, HER2-negative advanced breast cancer (DAWNA-2): a multicentre, randomised, double-blind,
placebo-controlled, phase 3 trial. Lancet Oncol. 2023; 24:646-57. https://doi.org/10.1016/s1470-
2045(23)00172-9.
17. Husereau D, Drummond M, Augustovski F, de Bekker-Grob E, Briggs AH, Carswell C, et al.
Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement:
Updated reporting guidance for health economic evaluations. Health Policy Open. 2022; 3:100063.
https://doi.org/10.1016/j.hpopen.2021.100063.
18. Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, et al. Consolidated Health
Economic Evaluation Reporting Standards (CHEERS) statement. The European Journal of Health
Economics. 2013; 14:367-72. https://doi.org/10.1007/s10198-013-0471-6.
19. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal
therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised
trials. Lancet. 2005; 365:1687-717. https://doi.org/10.1016/s0140-6736(05)66544-0.
20. Peart O. Metastatic Breast Cancer. Radiol Technol. 2017; 88:519m-39m.
21. Liu GE,editor.China guidelines for pharmacoeconomic evaluation. China Market Press. 2020.
22. National Bureau Of Statistics Of China. https://data.stats.gov.cn/search.htm?s=GDP. Accessed April
1, 2023.
23. Guyot P, Ades AE, Ouwens MJ, Welton NJ. Enhanced secondary analysis of survival data:
reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol. 2012;
12:9. https://doi.org/10.1186/1471-2288-12-9.
24. Latimer NR: Survival Analysis For Economic Evaluations Alongside Clinical Trials - Extrapolation with
Patient-Level Data. National Institute for Health and Care Excellence (NICE) Decision Support Unit
Technical Support; 2013.
25. Shenzhen pharmaceutical trading platform.https://login.qywgpo.com/login.html. Accessed 20
November 2022.
26. Buehler AM, Castilho G, Dionne P-A, Stefani S. Cost-effectiveness of ribociclib plus letrozole versus
palbociclib plus letrozole or letrozole as monotherapy in first-line treatment of postmenopausal
women with HR+/HER2− locally advanced or metastatic breast cancer: a Brazilian private payer
perspective. Ther Adv Med Oncol. 2021; 13:1-16. https://doi.org/10.1177/17588359211000593.
27. Huang X, Lin S, Rao X, Zeng D, Wang H, Weng X, et al. First-line Treatment with Ribociclib plus
Endocrine Therapy for Premenopausal Women with Hormone-receptor-positive Advanced Breast
Cancer: A Cost-effectiveness Analysis. Clin Breast Cancer. 2021; 21:e479-e88.
https://doi.org/10.1016/j.clbc.2021.01.019.
Page 13/17
28. Liao XZ, Shi JF, Liu JS, Huang HY, Guo LW, Zhu XY, et al. Medical and non‐medical expenditure for
breast cancer diagnosis and treatment in China: a multicenter cross‐sectional study. Asia Pac J Clin
Oncol. 2017; 14:167-78. https://doi.org/10.1111/ajco.12703.
29. Mistry R, May JR, Suri G, Young K, Brixner D, Oderda G et al. Cost-Effectiveness of Ribociclib plus
Letrozole Versus Palbociclib plus Letrozole and Letrozole Monotherapy in the First-Line Treatment of
Postmenopausal Women with HR+/HER2- Advanced or Metastatic Breast Cancer: A U.S. Payer
Perspective. J Manag Care Spec Pharm. 2018; 24:514-23.
https://doi.org/10.18553/jmcp.2018.24.6.514.
30. Rugo HS, Finn RS, Diéras V, Ettl J, Lipatov O, Joy AA, et al. Palbociclib plus letrozole as first-line
therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced
breast cancer with extended follow-up. Breast Cancer Res Treat. 2019; 174:719-29.
https://doi.org/10.1007/s10549-018-05125-4.
31. Stellato D, Thabane ME, Chandiwana D, Park J, Delea TE. Cost Effectiveness of Ribociclib Plus a
Nonsteroidal Aromatase Inhibitor in Pre-/Perimenopausal, HR+ and HER2− Advanced Breast Cancer:
A Canadian Healthcare Perspective. Pharmacoeconomics. 2021; 39:853-67.
https://doi.org/10.1007/s40273-021-01028-3.
32. Bank of China. Foreign Exchange Rate. https://www.boc.cn/sourcedb/whpj/. Accessed November 8 ,
2022.
33. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization
for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international
clinical trials in oncology. J Natl Cancer Inst. 1993; 85:365-76. https://doi.org/10.1093/jnci/85.5.365.
34. Sprangers MA, Groenvold M, Arraras JI, Franklin J, te Velde A, Muller M, et al. The European
Organization for Research and Treatment of Cancer breast cancer-specific quality-of-life
questionnaire module: first results from a three-country field study. J Clin Oncol. 1996; 14:2756-68.
https://doi.org/10.1200/jco.1996.14.10.2756.
35. Goetz MP, Martin M, Tokunaga E, Park IH, Huober J, Toi M, et al. Health-Related Quality of Life in
MONARCH 3: Abemaciclib plus an Aromatase Inhibitor as Initial Therapy in HR+, HER2− Advanced
Breast Cancer. Oncologist. 2020; 25:e1346-e54. https://doi.org/10.1634/theoncologist.2020-0084.
36. Lloyd A, Nafees B, Narewska J, Dewilde S, Watkins J. Health state utilities for metastatic breast
cancer. Br J Cancer. 2006; 95:683-90. https://doi.org/10.1038/sj.bjc.6603326.
37. Briggs AH, Weinstein MC, Fenwick EAL, Karnon J, Sculpher MJ, Paltiel AD. Model Parameter
Estimation and Uncertainty Analysis. Med Decis Making. 2012; 32:722-32.
https://doi.org/10.1177/0272989x12458348.
38. Zeng N, Han J, Liu Z, He J, Tian K, Chen N. CDK4/6 Inhibitors in the First-Line Treatment of
Postmenopausal Women with HR+/HER2− Advanced or Metastatic Breast Cancer: An Updated
Network Meta-Analysis and Cost-Effectiveness Analysis. Cancers. 2023; 15:3386.
https://doi.org/10.3390/cancers15133386.

Page 14/17
Figures

Figure 1

the Markov state transition model.

Figure 2

Page 15/17
Tornado plot generated in the one-way deterministic sensitivity analysis. Only the top 12 most influential
parameters are presented. PFS progression-free survival, PD progressed disease, WTP willingness-to-pay,
QALY quality-adjusted life-year, ICER Incremental cost-efectiveness ratio.

Figure 3

Cost-effectiveness plane generated in the probabilistic sensitivity analysis. WTP, willingness-to-pay.

Page 16/17
Figure 4

The cost-effectiveness acceptability curve for dalpiciclib plus letrozole versus abemaciclib plus letrozole.
QALY quality-adjusted life-year.

Page 17/17