First-line Treatment Of Postmenopausal Women Research Articles

446P 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

446P 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

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.

(1) Background: This study aimed to conduct a NMA and CEA combined study to compare the effectiveness and cost-effectiveness of different CDK4/6 inhibitors (Abem, Palbo, and Ribo) plus NSAI with placebo plus NSAI in the first-line treatment of postmenopausal women with HR+/HER2- ABC from the perspective of payers in China. (2) Methods: Studies which evaluated CDK4/6 inhibitors plus NSAI for HR+/HER2- ABC were searched. A Bayesian NMA was carried out and the main outcomes were the hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS). The costs and efficacy of first-line therapies for HR+/HER2- ABC were evaluated using the Markov model. The main outcomes in the CEA were incremental cost-utility ratios (ICURs), incremental monetary benefit (INMB), and incremental net-health benefit (INHB). The robustness of the model was assessed by one-way, three-way, and probabilistic sensitivity analyses. Then, we further simulated the impact of different prices of CDK4/6 inhibitors on the results. (3) Results: Seven studies involving 5347 patients were included in the NMA. The three first-line CDK4/6 inhibitors plus NSAI groups provided significant PFS and OS superiority to NSAI alone. Abem + NSAI represented a significant statistical advantage onPFS (HR 0.74, 95% CI 0.61-0.90, p = 0.009) and indicated a trend of being the best OS benefit compared to the placebo + NSAI group (HR 0.89, 95% CI 0.72-1.08). The Abem + NSAI, Palbo + NSAI, and Ribo + NSAI groups resulted in additional costs of $12,602, $20,391, and $81,258, with additional effects of 0.38, 0.31, and 0.30 QALYs, respectively, leading to an ICUR of $33,163/QALY, $65,777/QALY, and $270,860/QALY. Additional pairwise comparisons showed that Abem + NSAI was the only cost-effective option in three CDK4/6 inhibitors plus NSAI groups at a willingness-to-pay (WTP) of $38,029/QALY. The sensitivity analyses showed that the proportion of receiving subsequent CDK4/6 inhibitors and the cost of Abem significantly influenced the results of Abem + NSAI compared with placebo + NSAI. (4) Conclusion: From the perspective of Chinese payers, Abem + NSAI was a cost-effective treatment option compared with placebo + NSAI at the WTP of $38,029/QALY, since only the ICUR of $33,163/QALY of Abem + NSAI was lower than the WTP of $38,029/QALY in China (2022). The Palbo + NSAI and Ribo + NSAI groups were not cost-effective unless drug prices were adjusted to 50% or 10% of current prices ($320.67 per cycle or $264.60 per cycle). (5) Others: We have prospectively registered the study with the PROSPERO, and the PROSPERO registration number is CRD42023399342.

Cost-effectiveness of ribociclib versus palbociclib in combination with an aromatase inhibitor as first-line treatment of postmenopausal women with HR+/HER2− advanced breast cancer: analysis based on final OS results of MONALEESA-2 and PALOMA-2

Background and AimsCombination of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor and an aromatase inhibitor is the standard of care first-line (1L) treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC). Updated clinical data have become available from the MONALEESA-2 and PALOMA-2 trials for ribociclib and palbociclib, respectively. This analysis with updated data assessed the cost-effectiveness of ribociclib versus palbociclib, both in combination with letrozole, in the setting of 1L therapy of postmenopausal women with HR+/HER2− ABC, from a United Kingdom (UK) National Health Service perspective.MethodsA three state (progression-free, progressed disease, and death) partitioned survival model with a 1-month cycle was developed. Clinical data were derived from MONALEESA-2 (NCT01958021) and PALOMA-2 (NCT01740427). The treatment effect was modeled using hazard ratios (HRs) for progression-free survival and overall survival derived through a matched-adjusted indirect comparison. Trial data and published literature were used to derive utility values. Cost inputs included drug acquisition, disease monitoring, subsequent therapies, and adverse events. Costs and outcomes were discounted by 3.5%, over a 40-year lifetime horizon. One-way and probabilistic sensitivity analyses were performed.ResultsRibociclib dominated palbociclib, and was both overall cost saving (−£3,273) and more effective (+1.251 quality-adjusted life years [QALYs]). Ribociclib total drug costs were £17,156 lower than palbociclib. At a £30,000 per QALY willingness-to-pay threshold, the probability of ribociclib being cost-effective was almost 100%. Ribociclib remained cost-effective when varying HRs, utilities, drug cost, and health state costs.ConclusionsRibociclib is both cost-saving and cost-effective compared with palbociclib for the 1L treatment of postmenopausal women with HR+/HER2− ABC in the UK.

Adjuvant aromatase inhibitor treatment worsens depressive symptoms and sleep quality in postmenopausal women with localized breast cancer: A one-year follow-up study

First-line treatment in postmenopausal women with estrogen- and/or progesterone-positive breast cancer consists of aromatase inhibitors (AROi). The ability of AROi to promote or worsen cognitive function, depressive symptoms, sleep quality and performance in basic activities of daily life as primary and concomitant outcomes in long longitudinal studies in post-menopausal women has been seldom investigated. This study is a cohort trial which aimed to determine if there were differences in cognitive function assessment, depressive symptoms, and sleep quality after 1 year under AROi treatment and to determine the interrelations between these symptoms. Methods: A prospective 1-year longitudinal study was performed in a representative sample of tertiary hospital. Women with localized breast cancer newly treated with AROi therapy were evaluated for cognitive functions, depressive symptoms, sleep problems and ability to perform basic activities of the daily life at baseline and after 6 months and 12 months under adjuvant AROi treatment. Results: Analysis of cognitive functions by the Mini-Mental State Examination (MMSE) scores did not show significantly worsening under AROi treatment after 6 months and 12 months of treatment compared to the baseline. Analysis of depressive symptoms with the Geriatric Depression Scale and sleep quality with the Athens Insomnia Scale (AIS) scores showed significant (p < 0.05) changes after 6 and 12 months of treatment with AROi, with women describing more depressive symptoms and more sleep disturbances. Conclusions: Our study found impairments in sleep quality and an increase in depressive symptoms, which has important implications for clinicians as they impair quality of life and adherence to treatment.

EE372 Cost-Utility of Ribociclib As the First-Line Treatment in Postmenopausal Women with Hormone Receptor Positive and Human Epidermal Growth Factor Receptor-2 Negative Advanced/Metastatic Breast Cancer in Colombia

To estimate the cost-utility of the currently approved Cyclin-Dependent Kinase 4 and 6 Inhibitors (CDK4/6i) as the first-line treatment in postmenopausal women with Hormone Receptor positive (HR+) and Human Epidermal Growth Factor Receptor-2 negative (HER2-) advanced/metastatic breast cancer, from the perspective of the Colombian health system.

Aromatase Inhibitor-Induced Carpal Tunnel Syndrome and Stenosing Tenosynovitis: A Systematic Review.

Although aromatase inhibitors are the first-line treatment in postmenopausal women with hormone receptor-positive breast cancer, there is increasing evidence that they can induce carpal tunnel syndrome and stenosing tenosynovitis. This systematic review summarizes the risk factors, incidence, and management for patients with aromatase inhibitor-induced carpal tunnel syndrome and stenosing tenosynovitis compared to tamoxifen or placebo. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided systematic review of PubMed/MEDLINE, Ovid Embase, and the Cochrane Central Register of Controlled Trials was conducted (to March 19, 2020), supplemented with Google Scholar, Plastic and Reconstructive Surgery, and The Journal of Hand Surgery. Two reviewers independently completed the primary and secondary screens and the quality appraisal. This study reviewed 577 abstracts and included 19 studies. Risk factors for aromatase inhibitor-induced carpal tunnel syndrome or stenosing tenosynovitis included hormone replacement therapy before trial entry, history of musculoskeletal symptoms, age younger than 60 years, prior chemotherapy, and body mass index greater than 25 kg/m2. The incidence can be increased up to 10 times compared to tamoxifen. Patient discontinuation of aromatase inhibitor treatment because of carpal tunnel syndrome and stenosing tenosynovitis was reported. Nonsurgical management led to complete resolution of carpal tunnel syndrome symptoms in up to 67 percent of cases. Although most aromatase inhibitor-induced stenosing tenosynovitis original studies were low quality, all recommended surgical release for symptom resolution. This study provides current knowledge of the associated risk factors, management options, and quality of literature for aromatase inhibitor-induced carpal tunnel syndrome and stenosing tenosynovitis. Early recognition can prevent self-discontinuation of an aromatase inhibitor and long-term sequelae of poorly treated carpal tunnel syndrome and stenosing tenosynovitis.

Pharmacoeconomic evaluations of CDK4/6 inhibitors plus endocrine therapy for advanced hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) breast cancer: a systematic review.

BackgroundHormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2−) breast cancer is the most common molecular subtype of breast cancer in many countries, and endocrine therapy remains a mainstay in its treatment. Cyclin-dependent kinase (CDK) 4/6 inhibitors are a new class of targeted agents administered orally that are recommended being used in combination with endocrine therapy as first and second line treatments for advanced HR+/HER2− breast cancer. However, their high prices largely hinder using these drugs in real world settings. To offer a new basis for future research, we investigated the cost-effectiveness of combinations of CDK4/6 inhibitors with endocrine therapy in the treatment of advanced HR+/HER2− breast cancer.MethodsWe systematically searched several frequently used databases and identified economic evaluations published from February 2015 to April 2021. The systematic review was performed after retrieving the literatures and extracting data based on inclusion and exclusion criteria. The quality of each selected economic evaluation was assessed by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS).ResultsThe literature search yielded 161 articles, among which fourteen studies (15 articles) with CHEER scores ranging from 58.33% to 87.50% entered the final analysis. Markov models were used in most studies. Based on the currently available data, CDK4/6 inhibitors plus endocrine therapy were less cost-effective in first- or second-line treatment of patients with HR+/HER2− advanced breast cancer. However, ribociclib plus letrozole was more cost-effective than palbociclib plus letrozole in the first-line treatment of postmenopausal women. The economic impacts of CDK4/6 inhibitors plus endocrine therapy in non-postmenopausal patients or second-line therapy cannot be fully evaluated due to the limited number of studies. The three most common factors affecting economic outcomes were the prices of CDK4/6 inhibitors, hazard ratios for progression-free survival and overall survival, and health status utility values.DiscussionCDK4/6 inhibitors plus endocrine therapy have shown significantly improved efficacy outcomes in HR+/HER2− metastatic breast cancer (mBC)/advancer breast cancer (ABC) first-line and second-line treatment for endocrine-sensitive and endocrine-resistant populations, while more potential fields including neoadjuvant and adjuvant settings are being identified to benefit a wider range of breast cancer patients. Meanwhile, risk of severe adverse events that more likely to happen in patients treated with CDK4/6 inhibitors can lead to reduced life quality and higher medical costs patients need to afford. The adverse drug reaction related cost in several economic burden studies were explored to be primarily driven by hospitalizations and outpatient, and assessment of cost associated with CDK4/6 inhibitors adverse events is worth further developing. Drug wastage costs were found higher in palbociclib regimen than ribociclib regimen due to different dosing patterns. Moreover, current economic evaluations showed that ribociclib plus letrozole had better economic benefits than palbociclib plus letrozole for first-line treatment of postmenopausal women with HR+/HER2− ABC.

POSA116 Cost-Utility of Ribociclib As the First-Line Treatment in Postmenopausal Women with Advanced/Metastatic Breast Cancer, Hormone Receptor Positive and Human Epidermal Growth Factor Receptor-2 Negative in Colombia

To estimate the cost-utility of ribociclib as the first-line treatment in postmenopausal women with advanced/metastatic breast cancer, Hormone Receptor positive (HR+) and HER2-, from the perspective of the Colombian health system. A partitioned survival model was built with pre-progression, post-progression and death health states, according to the areas under the curve for the survival functions, with a 40-year time horizon. Direct medical costs for medicines and their administration, monitoring, handling of adverse events and terminal care were included; a local expert validated resource usage. The sources of costs were price control circulars, SISMED, ISS and SOAT tariff manuals, and the database of sufficiency (values in USD 2021: 1 USD = 3,770.9 COP). The probabilities of the events were based on a systematic review and the hazard ratios of survival were estimated with an indirect comparison meta-analysis. Health utility values were extracted from the literature. A 5% discount rate was applied for outcomes and costs. Health effects were valued as Quality Adjusted Life Years (QALY). Cost-effectiveness was analyzed against a range of willingness to pay thresholds in a probabilistic sensitivity analysis type acceptability curve. In the base case, average values per patient are: USD$ 22,919.90/2.92 QALY for fulvestrant, USD$ 79,385.04/3.17 QALY for ribociclib+letrozole, USD$ 84,735.61/3.17 QALY for palbociclib+letrozole and USD$ 110,699.86/3.47 QALY for ribociclib+fulvestrant. Ribociclib+letrozole is a dominant alternative to palbociclib+letrozole and between a willingness to pay of USD$ 0.0-84,064 is the alternative with the highest probability of cost-effectiveness. Ribociclib+fulvestrant has the greater effectiveness among all alternatives and has extended dominance over ribociclib+letrozole; however, its incremental cost-effectiveness ratio exceeds the three times gross domestic product per capita threshold (USD$ 16,728.36). Ribociclib+letrozole is a cost-effective and cost-saving alternative to the Colombian health system, as a first-line treatment in postmenopausal women with advanced/metastatic breast cancer, HR+ and HER2-.

Real-world data of fulvestrant as first-line treatment of postmenopausal women with estrogen receptor-positive metastatic breast cancer

Goals of endocrine therapy for advanced breast cancer (ABC) include prolonging survival rates, maintaining the quality of life, and delaying the initiation of chemotherapy. We evaluated the effectiveness of fulvestrant as first-line in patients with estrogen receptor (ER)-positive ABC with relapse during or after adjuvant anti-estrogenic therapy in real-world settings. Retrospective, observational study involving 171 postmenopausal women with ER-positive ABC who received fulvestrant as first-line between January 2011 and May 2018 in Spanish hospitals. With a median follow-up of 31.4 months, the progression-free survival (PFS) with fulvestrant was 14.6 months. No differences were seen in the visceral metastatic (14.3 months) versus non-visceral (14.6 months) metastatic subgroup for PFS. Overall response rate and clinical benefit rate were 35.2% and 82.8%. Overall survival was 43.1 months. The duration of the clinical benefit was 19.2 months. Patients with ECOG performance status 0 at the start of treatment showed a significant greater clinical benefit rate and overall survival than with ECOG 1–2. Results in real-world settings are in concordance with randomized clinical trials. Fulvestrant continues to demonstrate clinical benefits in real-world settings and appears be well tolerated as first-line for the treatment of postmenopausal women with ER-positive ABC.

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.

Background:The global burden of breast cancer (BC) is high, especially in advanced stages. CDK 4/6 inhibitors represent a paradigm shift in the treatment of advanced BC HR+/HER2−, given the clinically and statistically significant gain in overall survival associated with this new class of medications. Nevertheless, as an innovation, the incorporation of these drugs impacts healthcare budgets, requiring cost-effectiveness analyses for decision-making. The aim of this study was to evaluate the cost-effectiveness of ribociclib plus letrozole compared with palbociclib plus letrozole or letrozole as monotherapy for first-line treatment of postmenopausal women with HR+/HER2− locally advanced or metastatic BC (aBC) from a Brazilian private healthcare system perspective.Methods:A model including progression-free survival (PFS), progressed disease, and death health states was used to simulate lifetime costs and outcomes. PFS and overall survival were derived from the MONALEESA-2 trial (lifetime horizon). Healthcare costs included drug acquisition and monitoring, subsequent therapies, adverse events, and end-of-life costs. Effectiveness was measured in quality-adjusted life-years (QALYs). Deterministic and probabilistic sensitivity analyses were performed.Results:The total cost of treatment with ribociclib plus letrozole was USD 72,091.82 versus USD 92,749.64 for palbociclib plus letrozole. Total QALYs were 3.30 and 3.16, respectively. Base-case analysis showed ribociclib as dominant over palbociclib in first-line treatment of women with HR+/HER2− aBC, associated with cost savings and QALY gains. The total cost of treatment with ribociclib plus letrozole was USD 83,058.73 versus USD 29,215.10 for letrozole. Total QALYs were 3.84 and 2.61, respectively. Compared with letrozole, ribociclib plus letrozole was associated with an incremental cost of USD 53,843.64 and an incremental QALY gain of 1.23, with incremental cost-effectiveness ratio of USD 43,826.91 per QALY gained.Conclusions:As demonstrated by the cost-effectiveness dominance over palbociclib, ribociclib results in savings when used as first-line treatment in postmenopausal women with HR+/HER2− aBC, warranting incorporation in the private healthcare system.

Half-dose fulvestrant plus anastrozole as a first-line treatment for hormone receptor-positive metastatic breast cancer: a cost-effectiveness analysis.

ObjectiveThe S0226 trial demonstrated that the combination of half-dose fulvestrant (FUL) and anastrozole (ANA) (F&A) caused a significant improvement in overall survival (OS) versus ANA monotherapy for first-line treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer (PMW-MBC (HR+)). The objective of this study was to evaluate the cost-effectiveness of F&A in the first-line treatment for PMW-MBC (HR+) in China.DesignWe constructed a Markov model over a life-time horizon. The clinical outcomes and utility data were obtained from published literature. Cost data were obtained from official Chinese websites. Sensitivity analyses were performed to test result uncertainty.SettingChinese healthcare system perspective.PopulationA hypothetical cohort of adult patients presenting with PMW-MBC (HR+).InterventionsF&A compared with full-dose FUL and ANAmonotherapy.Main outcome measuresThe main outcome of this study was the incremental cost-effectiveness ratio (ICER) and quality-adjusted life-years (QALY).ResultsANA was estimated to have the lowest cost and minimum life-years. The ICER of F&A versus ANA was US$15 665.891/QALY with incremental cost and QALY of US$12 401.120 and 0.792, respectively, which was less than the willingness-to-pay of US$29 383/QALY. Compared with F&A, FUL yielded a higher cost and a shorter lifetime; hence, it was identified as a dominated strategy. The univariate sensitivity analysis indicated the price of FUL was the most influential factor in our study. The probability that F&A was cost-effective at a threshold of US$29 383/QALY in China was 86.5%.ConclusionF&A is a cost-effective alternative to FUL and ANA monotherapy for the first-line treatment of PMW-MBC (HR+) in China. F&A is a promising first-line treatment for PMW-MBC (HR+), and more research is needed to evaluate the economy of using F&A in other countries.

Abstract P1-19-33: Real-world efficacy of ribociclib + aromatase inhibitor, or endocrine monotherapy, or chemotherapy as first-line treatment in postmenopausal women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: Second interim analysis from the RIBANNA study

Abstract Background: Ribociclib (RIB, a selective CDK4/6 inhibitor) plus an aromatase inhibitor (AI) or fulvestrant (FUL) is approved for the treatment of premenopausal and postmenopausal women with HR+/HER2- advanced breast cancer (aBC). Real-world evidence for the effectiveness, safety and tolerability of RIB + AI/FUL in routine clinical practice is needed to support the use of this combination. Methods: RIBANNA is a noninterventional study ongoing in Germany since October 2017. Premenopausal and postmenopausal patients (N=3020) treated with RIB + AI/FUL, or endocrine monotherapy (ET), or chemotherapy (CT) as first-line treatment for HR+/HER2- aBC in accordance with German guidelines were included. Data are being collected from clinical practice in all 3 cohorts. Further lines of treatment are noted to examine outcomes of sequential therapy. Results: For the first interim analysis, 461 patients were enrolled until October 9, 2018, while full analysis set comprised 282 patients (Table 1). The first-line mean daily dose of RIB was 382 mg including and 540 mg excluding dose interruptions, respectively. RIB was prescribed mainly in combination with letrozole (83%), anastrozole (8%), and exemestane (7%); ET included nonsteroidal AI (64%), selective estrogen receptor degrader (25%), selective estrogen receptor modulator (7%), and steroidal AI (5%); CT included taxane-based monotherapy (30%) or combination therapy (27%), other monotherapy (23%) or other combination therapy (13%), and anthracycline-based combination therapy (5%). Conclusion: RIBANNA study showed diverse population characteristics among patients who received RIB treatment in a real-world setting. Based on the baseline demographics data, RIB (CDK4/6 inhibitor) treatment was found to be very well adopted among premenopausal and postmenopausal patients with HR+/HER2- aBC. The second interim analysis is planned for October 2019. Updated baseline data of approximately 1200 to 1300 patients and information on safety and dose modification for first-line patients from all cohorts will be presented. Table 1. Baseline demographic characteristicsTotal (N = 282)RIB + AI (n = 216)Endocrine therapy (n = 26)Chemotherapy (n = 40)Mean age, years (SD)67 (11)67 (10)71 (12)62 (10)Mean time since initial diagnosis, years5.45.56.53.9T stage at initial diagnosis, n (%)T0+T161 (100)48 (79)6 (10)7 (11)T2-T4198 (100)149 (75)17 (9)32 (16)N stage at initial diagnosis, n (%)N0+N1186 (100)144 (77)16 (9)26 (14)N2+N364 (100)48 (75)5 (8)11 (17)M stage at initial diagnosis, n (%)M0156 (100)121 (78)14 (9)21 (13)M1101 (100)75 (74)9 (9)17 (17)Locally advanced, n (%)101 (100)73 (72)9 (9)19 (19)Metastatic, n (%)101 (100)75 (74)9 (9)17 (17)Metastatic location, n (%)CNS, liver, lungs119 (100)96 (81)1 (1)22 (18)Bone only84 (100)62 (74)17 (20)5 (6)Skin, lymph nodes, other52 (100)37 (71)6 (11)9 (17) Citation Format: Achim Wöckel, Pawel Basiora, Michael Bohlmann, Thomas Decker, Jörg Falbrede, Peter Fasching, Helmut Forstbauer, Tobias Hesse, Oliver Hoffmann, Christian Jackisch, Anna Kaczerowsky, Ralf Lorenz, Kerstin Lüdtke-Heckenkamp, Diana Lüftner, Frederik Marmé, Thomas Mueller, Christoph Mundhenke, Arnd Nusch, Volker Petersen, Gabriele Prange-Krex, Toralf Reimer, Thomas Resch, Christian Roos, Oliver Tomé, Anja Weishap. Real-world efficacy of ribociclib + aromatase inhibitor, or endocrine monotherapy, or chemotherapy as first-line treatment in postmenopausal women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: Second interim analysis from the RIBANNA study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-33.

Real-world effectiveness of ribociclib + aromatase inhibitor, or endocrine monotherapy, or chemotherapy as first-line treatment in postmenopausal women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: Baseline data from the RIBANNA study.

e12520 Background: Ribociclib, a selective CDK4/6 inhibitor, in combination with an aromatase inhibitor (AI) is approved for the treatment of HR+/HER2- advanced breast cancer (aBC) (locally advanced or metastatic). Real-world evidence for the effectiveness, safety and tolerability of ribociclib + AI in routine clinical practice is needed to support its use. Methods: RIBANNA (CLEE011ADE03) is a non-interventional study running in Germany since October 2017 involving up to 3020 postmenopausal patients receiving ribociclib + AI, endocrine monotherapy (ET), or chemotherapy (CT) as first-line treatment for HR+/HER2- aBC, prescribed in line with German guidelines. Data are collected from clinical practice in all three cohorts. Further lines of treatment are documented to examine outcomes of sequential therapy. Results: 461 patients enrolled to October 9, 2018 (Table). First-line mean daily ribociclib dose was 382 mg including and 540 mg excluding dose interruptions; mean duration of exposure to ribociclib: 128 days. Ribociclib was given in combination with anastrozole (8%), exemestane (7%), and letrozole (83%); ET comprised a selective estrogen receptor degrader (25%), nonsteroidal AI (64%), steroidal AI (5%), and a selective estrogen receptor modulator (7%); CT included taxane-based monotherapy (30%) or combination therapy (27%), anthracycline-based combination therapy (5%), other monotherapy (23%) or other combination therapy (13%). Conclusions: Population characteristics from the RIBANNA study show a diverse group of patients from a real-world setting of ribociclib treatment. Baseline demographics and characteristics. Clinical trial information: CLEE011ADE03. [Table: see text]

Abstract P2-08-34: The network metanalysis of data from PALOMA 2, MONALEESA 2, MONARCH 3, FALCON, SWOG and FACT trials: Progression free survival (PFS) benefit from first-line endocrine-based therapies in postmenopausal women with HR+ HER2- metastatic breast cancer (MBC) according to different prognostic subgroups

Abstract Background The three classes of Cycline Dependend Kinase (CDK) 4/6 inhibitors, Palbociclib (P), Ribociclib (R) and Abemaciclib (A), in combination with non-Steroidal Aromatase Inhibitors (nSAIs) showed improvement on Progression Free Survival (PFS) in patients with HR+/HER2- MBC compared to AIs monotherapy. Fulvestrant (F) also showed a PFS benefit over AIs in first-line setting of endocrine naive patients (pts) which was even greater in pts whithout visceral disease. The absence of direct comparison between F and CDK 4/6 combination therapies and their less favorable toxicity profile generated great interest in the identification of a specific subgroup of pts based on clinical and pathological factors for decision-making in the use of endocrine monotherapy. This analysis combines data from six randomized phase III trials investigating the role of endocrine-based therapies in the first-line setting of HR+/HER2- MBC to identify clinical factors in the choice among available drugs. Methods A Bayesian network meta-analysis was carried out for PFS; Hazard Ratio (HR) and 95% CI were reported. Potential treatment effect modifying covariates were investigated using sub-group analysis, stratifying by age, ECOG, ethnicity, prior chemotherapy or endocrine therapy exposure, measurable disease at the time of metastasis occurrence, visceral or bone only disease, time from the initial diagnosis of breast cancer to the metastasis onset. Data analysis was performed using R Statistical Software version 3.5.0 Results In the absence of direct comparison between CDK 4/6 inhibitors + nAIs and F endocrine-based therapies, all these therapeutic options resulted in significant PFS benefit compared to nAIs monotherapy (HR: 0.74; 95% CI 0.67-0.80). However, among the three classes of CDK 4/6 inhibitors and F a significant longer PFS was observed according to some clinical-pathological factors as followed reported: from P + nAIs in “bone only” disease (HR 0.47; CI 0.25-0.86); from A + nAis in “de novo” subgroup (HR 0.60; CI 0.37-0.97), in “Asian” population (HR 0.37; CI 0.16-0.85) and “non visceral” disease (HR 0.48 CI 0.25-0.89); from R + nAIs in “de novo” subgroup (HR 0.55; CI 0.32-0.95) and in “visceral” disease (HR 0.66 CI 0.45-0.96); from all the three combination strategies (A, P and R) in “prior endocrine” exposure subgroup (HR 0.47 CI 0.25-0.87; HR 0.60 CI 0.45-0.80; HR 0.64 CI 0.41-1.0, respectively). Even though no significant PFS benefit was observed in the remaining subgroups, combined CDK 4/6 strategies appeared more effective than F according to relative HR. Conclusions CDK 4/6 inhibitors endocrine-based therapies as first-line treatment for postmenopausal women with HR+/HER2- MBC showed PFS improvement, regardless of prognostic subgroup and additionally advantage was emerged by indirect comparison with F. Further direct comparative studies are needed to explore greater benefits from different therapeutic options. Citation Format: Rossi V, Giannarelli D, Berchialla P, Montemurro F, Ferretti G, Nistico' C, Vigna L, Cognetti F, Fabi A. The network metanalysis of data from PALOMA 2, MONALEESA 2, MONARCH 3, FALCON, SWOG and FACT trials: Progression free survival (PFS) benefit from first-line endocrine-based therapies in postmenopausal women with HR+ HER2- metastatic breast cancer (MBC) according to different prognostic subgroups [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-34.

Addressing physician barriers to administering cyclin-dependent kinases 4 and 6 inhibitors in first-line treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer.

Combination therapy with a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor and an aromatase inhibitor (AI) for first-line treatment of postmenopausal women with advanced breast cancer (ABC) has demonstrated improvement in progression-free survival (PFS) over AI monotherapy without adding substantial toxicity. However, CDK4/6 inhibitor plus AI therapy is not uniformly used as first-line therapy for ABC, indicating that barriers to CDK4/6 inhibitor use exist. Such barriers may include the following perceptions: patients with bone-only metastases, with a long disease-free interval, or who are older may respond to AI monotherapy and may not benefit from a CDK4/6 inhibitor; tumor response rates may be lower and delayed with CDK4/6 inhibitor plus AI therapy than chemotherapy; the increased incidence of adverse events with CDK4/6 inhibitor plus AI therapy outweighs benefits; and the cost of CDK4/6 inhibitors may be prohibitive. Some of these barriers are addressed with data from follow-up analyses of CDK4/6 inhibitor trials, which have shown a PFS benefit of combination therapy in all subgroups assessed, including older patients, those with bone-only metastatic disease, and those with a long disease-free interval. Tumor response rates with CDK4/6 inhibitor plus AI therapy are comparable to those with first-line cytotoxic chemotherapy. Finally, adverse events associated with CDK4/6 inhibitor plus AI therapy are manageable and occur with decreasing severity during treatment, with similar reports of quality of life to those with AI monotherapy. These data support CDK4/6 inhibitor plus AI therapy as the standard of care in first-line treatment of ABC.

Cost-effectiveness analysis of ribociclib versus palbociclib in the first-line treatment of HR+/HER2- advanced or metastatic breast cancer in Spain.

PurposeThe aim of this study was to evaluate the cost-effectiveness of ribociclib compared to palbociclib, both in combination with letrozole, in the first-line treatment of postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer (ABC) from the perspective of the Spanish National Health System (NHS).Patients and methodsDisease progression was simulated with a partitioned survival model developed from the parameterization and extrapolation of survival curves of postmenopausal women with HR+/HER2− ABC from clinical trials with ribociclib or palbociclib, both in combination with letrozole. The model was structured on the basis of three health states (progression-free, progressed disease, and death), with a 1-month cycle length and inclusion of subsequent treatments administered for disease progression, over a time horizon of 15 years. Clinical, economic, and quality of life parameters were drawn from clinical trials and the literature. The use of resources and clinical practice in the Spanish setting was validated by a panel of experts. The Spanish NHS perspective was adopted, taking into account exclusively direct health costs from 2017 expressed in Euros. Drug prices used were the reported ex-factory prices. Uncertainty of the parameters and robustness of the results were evaluated using deterministic and probabilistic sensitivity analyses (2,000 iterations).ResultsThis cost-effectiveness analysis showed a greater benefit (0.437 and 0.285 life-years gained [LYGs] and quality-adjusted life years [QALYs] gained, respectively) and a slightly higher cost (€439.86) for ribociclib+letrozole compared to palbociclib+letrozole. The resulting incremental cost-effectiveness and cost-utility ratios were €1,007.69 per LYG and €1,543.62 per QALY gained, respectively. The results of the multiple sensitivity analyses showed limited dispersion of the outcomes, thus corroborating their robustness.ConclusionFrom the NHS perspective, considering the most commonly established willingness-to-pay thresholds in the Spanish setting, ribociclib+letrozole would represent a cost-effective therapeutic option compared to palbociclib+letrozole in the first-line treatment of HR+/HER2− ABC in postmenopausal women.

PRM134 - USING ADJUSTED INDIRECT COMPARISON IN HTA TO OVERCOME SHORT FOLLOW-UP TIME IN REGULATORY RANDOMIZED CONTROLED CLINICAL TRIALS: RIBOCICLIB AS FIRST-LINE THERAPY FOR HR-POSITIVE, ADVANCED BREAST CANCER

When assessing the value of innovative medicines Health Authorities are often faced with immature overall survival (OS) data from regulatory clinical trials. The aim of our study was to assess the OS benefits of ribociclib combined with letrozole (RIB+LTZ) for first-line treatment in postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease, using anchored adjusted indirect comparison with more mature data. We performed an anchored indirect comparison using simulated treatment comparison (STC) (PMID:25795232) which relay on regression methods to adjust for potential imbalance in effect modifiers (age, bone metastasis, previous chemotherapy, previous adjuvant endocrine therapy). We combined individual patient data (n=668) from the MONALEESA-2 trial (NCT01958021) with median follow-up of 15 months and aggregate data (n=916) from a phase III study of letrozole (LTZ) versus tamoxifen as first-line therapy of advanced breast cancer (PMID:12775735) with longer follow-up time (32 months). Different accelerated time failure models were tested to assess effect modifiers over OS. The Weibull AFT regression model was assumed not only because of its statistical properties (low AIC value) but also because of the clinical and biological plausibility of the extrapolated share of the survival beyond trial data observation. Indirect comparison with STC suggests a significantly 48% reduction in the risk of death for the use of RIB+LTZ relative to LTZ (HR=0.37; 95%CI: 0.34-0.39). Estimated adjusted median OS was 68 months for RIB+LTZ and 36 months for LTZ. The latter compares well with the observed median OS of 34 months (PMID: 12775735) and the former will only occur with longer follow-up in the MONALEESA-2 trial. Adjusted indirect comparison methods are useful to inform about early adoption of innovation in the absence of mature overall survival data from regulatory clinical trials.

282TiP - Real-world effectiveness of ribociclib + aromatase inhibitor, or endocrine monotherapy, or chemotherapy as first-line treatment in postmenopausal women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: The RIBANNA study

282TiP - Real-world effectiveness of ribociclib + aromatase inhibitor, or endocrine monotherapy, or chemotherapy as first-line treatment in postmenopausal women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: The RIBANNA study

First person: George Sledge, Jr, MD: Former ASCO president leads breast cancer research and mentors Stanford faculty.

First person: George Sledge, Jr, MD: Former ASCO president leads breast cancer research and mentors Stanford faculty.

Budget impact of including ribociclib in combination with letrozole on US payer formulary: first-line treatment of post-menopausal women with HR+/HER2− advanced or metastatic breast cancer

Objectives: The combination of a cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitor with the aromatase inhibitor letrozole is a safe and effective alternative to letrozole monotherapy for first-line hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer. This study evaluates the budget impact of using the CDK 4/6 inhibitor ribociclib plus letrozole as a first-line treatment option for postmenopausal women with HR+/HER2− advanced breast cancer, from a United States (US) payer perspective.Methods: A cohort-based budget impact model was used to calculate the incremental cost of introducing ribociclib plus letrozole over three years for the target population. The analysis compared two scenarios: treatment options excluding or including ribociclib plus letrozole. Market shares were derived from market research and the assumption was the introduction of ribociclib plus letrozole would only displace existing CDK-based therapies. Treatment duration was based on the median time to treatment discontinuation or median progression-free survival for first-line treatment, and on clinical trial data for second- and third-line treatment. Acquisition costs were based on wholesale acquisition costs and considered co-payment. Costs for drug administration and monitoring, subsequent therapy, and relevant adverse events were included.Results: Of 1 million insured members, 263 were eligible for CDK 4/6 inhibitor treatment. Cumulative total savings with ribociclib plus letrozole were $3.01M over three years, corresponding to a cumulative incremental cost saving of $318.11 per member treated per month.Conclusions: In the US, ribociclib plus letrozole represents a cost-saving first-line treatment option for postmenopausal women with HR+/HER2− advanced breast cancer.