Cost-effectiveness of palbociclib plus fulvestrant as second-line therapy of women with HR+/HER2- advanced breast cancer - A Chinese healthcare system perspective.

Aim: To evaluate the cost-effectiveness of palbociclib plus fulvestrant in the second-line treatment of women with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer based on the latest published follow-up data from the perspective of the Chinese healthcare system. Methods: In view of the PALOMA-3 trial, a Markov model was built for this purpose, which included three health states: progression-free survival (PFS), progressed disease (PD), and death. The cost and health utilities were mainly derived from the published literature. One-way sensitivity analysis and probabilistic sensitivity analysis were carried out to verify the robustness of the model. Results: In the base case analysis, compared with the placebo plus fulvestrant arm, the palbociclib plus fulvestrant arm yielded an additional 0.65 quality-adjusted life years (QALYs) (2.56 QALYs vs. 1.90 QALYs) with an incremental cost of $36,139.94 ($55,482.06 vs. $19,342.12), resulting an incremental cost-effectiveness ratio (ICER) of $55,224.90/QALY, which was deeply higher than a willingness-to-pay (WTP) threshold of $34,138.28 per QALY in China. The results of one-way sensitivity analysis indicated that the utility of PFS, cost of palbociclib, and cost of neutropenia had a great influence on the ICER. Conclusions: Palbociclib plus fulvestrant is unlikely to be cost-effective in comparison with placebo plus fulvestrant as second-line therapy of women with HR+/HER2- advanced breast cancer.

Cost-Effectiveness Analysis of Abemaciclib plus Fulvestrant versus Placebo plus Fulvestrant in Patients with Hormone Receptor-Positive, ERBB2-Negative Breast Cancer.

Purpose: Abemaciclib is a selective and potent small-molecule inhibitor of cyclin-dependent kinase 4 and 6 (CDK4 and CDK6) which is administered orally. Compared to placebo plus fulvestrant (PF), abemaciclib plus fulvestrant (AF) significantly improved progression-free survival (PFS) and overall survival (OS). However, an economic evaluation of these two treatments is currently lacking. The purpose of this article was to evaluate the cost-effectiveness of the two treatments for HR*, HER2- advanced breast cancer (ABC) in the USA. Methods: A Markov simulation model was constructed using data from a published clinical trial (MONARCH 2). The two simulated treatment strategies included AF or PF. Costs were obtained from the clinical trials and the website, and utility was derived from the published literature. Incremental cost-effectiveness ratios (ICERs) were calculated to compare the two treatment strategies. Results: The total costs were USD 400,377.43 and USD 89,937.77 for AF and PF treatment, respectively. The AF treatment produced 2.09 long-term quality-adjusted life years (QALYs), and the PF treatment produced 1.08 QALYs. Hence, patients who received AF treatment spent an additional USD 310,439.66 and generated an increase of 1.01 QALYs, resulting in an ICER of USD 307,366 per QALY. At current prices, AF was not cost-effective assuming a willingness-to-pay threshold of USD 150,000 per QALY gained. Conclusion: Despite significant gains in PFS over AF, it is not a cost-effective treatment for HR*, HER2- ABC in the USA at current drug prices.

Safety in Japanese Advanced Breast Cancer Patients Who Received Abemaciclib in MONARCH 2 and MONARCH 3: Assessment of Treatment-Emergent Neutropenia, Diarrhea, and Increased Alanine Aminotransferase and Aspartate Aminotransferase Levels.

Purpose: Our objective was to gain a better understanding of the safety of abemaciclib in Japanese patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Patients and Methods: Treatment-emergent adverse events (TEAEs) were assessed in pooled Japanese subpopulation data from two phase 3 studies assessing abemaciclib/placebo in combination with fulvestrant (MONARCH 2; M2) or non-steroidal aromatase inhibitors (MONARCH 3; M3). For common, clinically relevant TEAEs, event characteristics and management were summarized by study. Results: In the Japanese safety subpopulation (abemaciclib: N=101; placebo: N=46), all patients experienced ≥1 TEAE (Grade ≥ 3: abemaciclib, 71.3%; placebo, 23.9%; no Grade 5). Clinically relevant TEAEs that were more frequent in abemaciclib-treated Japanese patients compared to the overall safety populations included diarrhea (any grade, 95.0%; Grade ≥ 3, 12.9%), neutropenia (any grade, 75.2%; Grade 3-4, 35.6%), increased alanine aminotransferase (ALT; any grade, 39.6%; Grade 3-4, 14.9%), and increased aspartate aminotransferase (AST; any grade, 37.6%; Grade 3-4, 8.9%). Diarrhea was Grade ≤3 and successfully managed with medications (≥87%) and dose reductions (≤25%) and/or omissions (≤23.3%). Most Grade ≥2 diarrhea occurred in the first treatment cycle, declining thereafter. Neutropenia, the most common Grade ≥3 TEAE in abemaciclib-treated Japanese patients, was generally manageable with dose omissions (M2: 42.0%; M3: 23.1%) and/or reductions (M2: 16%; M3: 15.4%). Neutrophil counts plateaued after Cycle 2, recovering to pretreatment levels after discontinuation of abemaciclib. Hepatic events were managed with medication (≤21%) and dose adjustments (≤33.3%), with most Grade ≥2 events occurring in early treatment cycles. Discontinuation of any study treatment in Japanese patients occurred more frequently due to increased ALT/AST (M2: 9.1%/10.5%; M3: 16.7%/10.5%) compared with diarrhea (M2: 0%; M3: 2.8%) or neutropenia (M2: 0%; M3: 3.8%). Conclusion: Abemaciclib was well tolerated in Japanese patients in MONARCH 2 and MONARCH 3, with common, clinically relevant TEAEs manageable with appropriate interventions.

Cost-effectiveness analysis of ribociclib plus fulvestrant for hormone receptor-positive/human EGF receptor 2-negative breast cancer.

Aim: To evaluate the cost-effectiveness of ribociclib plus fulvestrant versus fulvestrant in hormone receptor-positive/human EGF receptor 2-negative advanced breast cancer. Materials & methods: A three-state Markov model was developed to evaluate the costs and effectiveness over 10 years. Direct costs and utility values were obtained from previously published studies. We calculated incremental cost-effectiveness ratio to evaluate the cost-effectiveness at a willingness-to-pay threshold of $150,000 per additional quality-adjusted life year. Results: The incremental cost-effectiveness ratio was $1,073,526 per quality-adjusted life year of ribociclib plus fulvestrant versus fulvestrant. Conclusions: Ribociclib plus fulvestrant is not cost-effective versus fulvestrant in the treatment of advanced hormone receptor-positive/human EGF receptor 2-negative breast cancer. When ribociclib is at 10% of the full price, ribociclib plus fulvestrant could be cost-effective.

Cost-Effectiveness of Ribociclib for Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer.

PURPOSE: Ribociclib has provided significant improvements in progression-free survival (PFS) and overall survival (OS) of postmenopausal patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). However, given the high cost of ribociclib, its value must be evaluated based on cost-effectiveness. Thus, we aimed to explore the cost-effectiveness of ribociclib for postmenopausal patients with HR-positive and HER2-negative ABC. METHODS: A comprehensive Markov model was developed to estimate the cost-effectiveness of ribociclib plus fulvestrant versus placebo plus fulvestrant as first-line treatment for HR-positive, HER2-negative ABC. Variables were estimated based on data from the randomized Phase III MONALEESA-3 trial. Ten-year values were estimated for quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Direct treatment costs were estimated from the perspective of a United States payer. One-way and probabilistic sensitivity analyses were conducted to confirm the model's robustness. RESULTS: Ribociclib plus fulvestrant increased the treatment cost by $382,172 and provided 0.47 QALYs, relative to fulvestrant alone, which corresponded to an ICER of $813,132 per QALY. Sensitivity analyses revealed that ribociclib was unlikely to be cost-effective even under the most favorable assumptions. When the cost of ribociclib was <$1,384, there was a >50% chance of cost-effectiveness at a willingness-to-pay threshold of $150,000/QALY. Subgroup analyses also confirmed that ribociclib was not cost-effective. CONCLUSION: At current drug prices in the United States, ribociclib is unlikely to be cost-effective for treating postmenopausal patients with HR-positive HER2-negative ABC. Despite the clinical benefits of ribociclib, its cost would need to decrease to provide more favorable economic outcomes.

Fulvestrant más inhibidor CDK 4/6 para el tratamiento de cáncer de mama metastásico con receptores hormonales positivos / HER2 negativo / Fulvestrant plus CDK 4/6 inhibitor for treating cancer of the hormone receptor-positive / HER2-negative metastatic breast

INTRODUCCIÓN: Este documento técnico se realiza a solicitud del Instituto Nacional de Enfermedades Neoplásicas; la cual motivó la realización de la pregunta PICO por parte de médicos y especialistas de la siguiente manera, P: pacientes adultas con cáncer de mama HR+/HER2- metastásico; I: Fulvestrant + inhibidor CDK4/6 (iCDK4/6); C: inhibidor de aromatasa; O: Sobrevida global, sobrevida libre de progresión, tasa de respuesta y eventos adversos. A. Cuadro clínico: El cáncer de mama es una enfermedad en la cual se forman células malignas en los tejidos de la mama, las cuales pueden diseminarse a través de la sangre o de los vasos linfáticos y llegar a otras partes del cuerpo formando metástasis. En Perú, el cáncer de mama es el tipo de cáncer más frecuente en mujeres (19,5%) y el sexto tipo de cáncer más letal en la población general. Aproximadamente, 60%-70% de los cánceres de mama tienen receptores hormonales positivos (HR+). El tratamiento del cáncer de mama HR+/HER2− metastásico se dirige a prolongar la supervivencia y mantener la calidad de vida, siendo la terapia endocrina considerada la piedra angular de tratamiento. B. Tecnología sanitária: Fulvestrant es un antagonista del receptor de estrógeno indicado en monoterapia o terapia combinada con un inhibidor CDK4/6 para el tratamiento del cáncer de mama avanzado HR+/HER2- en mujeres postmenopáusicas sin terapia endocrina previa o con progresión de la enfermedad después de terapia endocrina. Su mecanismo de acción se basa en la unión competitiva al receptor de estrógenos y la regulación negativa de la proteína ER en las células de cáncer de mama. Las reacciones adversas más comunes incluyen dolor en sitio de inyección, náuseas, dolor de huesos, artralgia, dolor de cabeza, dolor de espalda baja, fatiga, sofocos, vómitos, anorexia, astenia, tos, disnea y constipación. Fulvestrant cuenta con aprobación de la Food and Drug Administration (FDA) para el tratamiento del cáncer de mama HR+/HER2- metastásico desde el 2002. En Perú, cuenta con tres registros sanitarios vigentes. OBJETIVO: Describir la evidencia científica disponible sobre la eficacia y seguridad de fulvestrant asociado a un inhibidor CDK4/6 para el tratamiento del cáncer de mama HR+/HER2- metastásico. METODOLOGÍA: Se realizó una búsqueda sistemática en Medline (Pubmed), The Cochrane Library y LILACS utilizando la estrategia de búsqueda descrita en el Anexo 01. Ésta se complementó con la búsqueda de evidencia en páginas institucionales de agencias gubernamentales y buscadores genéricos. Se priorizó la identificación y selección de ensayos clínicos aleatorizados controlados, revisiones sistemáticas (RS) con o sin meta-análisis (MA) de ensayos clínicos aleatorizados controlados, guías de práctica clínica (GPC), evaluaciones de tecnología sanitaria (ETS) y evaluaciones económicas (EE) de América Latina. La calidad de la evidencia se valoró usando las siguientes herramientas: AMSTAR 2 para la valoración de la calidad de RS, la herramienta propuesta por la colaboración Cochrane para ensayos clínicos y AGREE II para valorar el rigor metodológico de las GPC. RESULTADOS: Resultados relacionados con la eficácia: En postmenopáusicas con cáncer de mama metastásico HR+/HER2- y progresión a terapia endocrina, se observó una reducción de la progresión de la enfermedad con fulvestrant+palbocilib (HR: 0,63; IC 95%: 0,54 a 0,75) y fulvestrant+abemaciclib (HR: 0,69; IC 95%: 0,61 a 0,78), comparado con exemestano. Asimismo, se observó un incremento en la probabilidad de alcanzar respuesta parcial o completa con fulvestrant + palbocilib (OR: 2,66; IC 95%: 1,13 a 6,27) y fulvestrant + abemaciclib (OR: 2,63; IC 95%: 1,25 a 5,56), en comparación con exemestano. Finalmente, se observó un incremento en las tasas de beneficio clínico con fulvestrant + palbocilib (OR: 2,07; IC 95%: 1,52 a 2,83) y fulvestrant + abemaciclib (OR: 1,59; IC 95%: 1,21 a 2,09), comparado con exemestano. Resultados relacionados con la seguridade: En mujeres postmenopáusicas con cáncer de mama metastásico HR+/HER2- y progresión a terapia endocrina previa, fulvestrant + palbocilib no incrementó el riesgo de discontinuación debido a eventos adversos, en comparación con anastrazol 1 mg, anastrazol 10 mg, letrozol 0,5 mg, letrozol 2,5 mg y exemestano 25 mg. Recomendaciones en GPC: Las GPC recomiendan en su mayoría el uso de inhibidores de aromatasa como primera línea de tratamiento. En segunda línea, las GPC europeas y de sociedades médicas recomiendan fulvestrant + inhibidor de CDK4/6 como alternativa de tratamiento, mientras que las GPC de Colombia y Chile no la incluyen en sus recomendaciones. CONCLUSIONES: No se identificaron estudios que comparen directamente fulvestrant + inhibidor CDK4/6 respecto a inhibidores de aromatasa. Asimismo, los análisis se realizaron en postmenopáusicas con progresión a terapia endocrina. Las conclusiones podrían no aplicar a premenopáusicas o en el contexto de primera línea de tratamiento. • Ninguna RS evaluó la sobrevida global, debiendo considerar si otros desenlaces intermedios como la sobrevida libre de progresión pueden ser considerados subrogados y valorar desde esta perspectiva el beneficio clínico neto de la tecnología En comparación con inhibidores de aromatasa (IA), la combinación de fulvestrant + iCDK4/6 redujo el riesgo de progresión de la enfermedad y mejoró las tasas de respuesta objetiva y beneficio clínico, sin diferencias en la discontinuación del tratamiento debido a EA. Las GPC recomiendan en su mayoría el uso de IA como primera línea. En segunda línea, las GPC europeas y de sociedades médicas recomiendan fulvestrant + iCDK4/6 como alternativa de tratamiento, mientras que las Colombia y Chile no la incluyen en sus recomendaciones. Las ETS de CONETEC e IETSI no recomiendan fulvestrant + palbociclib debido al impacto económico y alto nivel de incertidumbre acerca de su beneficio clínico neto. La ETS del NICE recomienda fulvestrant + iCDK4/6 solo en personas con progresión a terapia hormonal y en caso exemestano más everolimus sea la alternativa más apropiada a un iCDK 4/6.

First-line fulvestrant plus anastrozole for hormone-receptor-positive metastatic breast cancer in postmenopausal women: a cost-effectiveness analysis.

PURPOSE: In a recent randomized, open-label trial (S0226), the addition of fulvestrant to anastrozole therapy decreased the risk of progression and death in patients with hormone-receptor-positive metastatic breast cancer. However, the cost-effectiveness of incorporating fulvestrant into the first-line setting is unknown. METHODS: We developed a Markov model to assess the costs and clinical outcomes of fulvestrant plus anastrozole compared with anastrozole as a first-line therapy in a cohort of patients with advanced hormone-receptor-positive breast cancer. The transition probabilities were estimated from the fitted survival curves in the S0226 trial. Health care costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for fulvestrant plus anastrozole compared with anastrozole from US payer's perspective. RESULTS: Fulvestrant plus anastrozole led to an improvement of 0.11 QALYs compared with treatment with anastrozole alone. However, incorporating fulvestrant into the first-line therapy produced significantly higher health care costs ($72,496 vs. $38,959 for all eligible patients, and $73,728 vs. $37,239 for patients with no previous hormonal adjuvant therapy), resulting in ICERs of $300,564 and $194,450/QALY, respectively. Two-way sensitivity analysis showed that when the cost of fulvestrant decreased to $1.5/mg for all eligible patients or $3.5/mg for patients with no previous hormonal adjuvant therapy, at the perfect health in progression-free status, the ICER became $141,320 and $145,543 per QALY. CONCLUSION: Substituting fulvestrant as a first-line therapy for hormone-receptor-positive metastatic breast cancer is not cost-effective compared with anastrozole based on the willing-to-pay threshold of $150,000 per QALY.

Hormonal Therapy Resistant Estrogen-receptor Positive Metastatic Breast Cancer Cohort (HORSE-BC) Study : Current Status of Treatment Selection in Japan.

The Hormonal therapy resistant estrogen-receptor positive metastatic breast cancer cohort (HORSE-BC) study is a multicenter observational study evaluating the efficacy and safety of secondary endocrine therapy (ET) for postmenopausal cases of metastatic breast cancer (MBC) with poor response to primary ET. In this initial report we analyze the HORSE-BC baseline data to clarify the current status of treatment selection for MBC in Japan. Baseline data for the 50 patients enrolled in HORSE-BC were analyzed, including patient characteristics, types of secondary ET, and reasons for selecting secondary ET. Postoperative recurrence was detected in 84% of patients (42/50) and de novo stage IV breast cancer in 16% (8/50). Forty-one patients (41/50; 82%) received fulvestrant, 5 patients (10%) received selective estrogen receptor modulators (SERMs), 3 patients (6%) received ET plus a mammalian target of rapamycin (mTOR) inhibitor, and 1 patient received an aromatase inhibitor (AI) as the secondary ET. Forty-five patients selected their secondary ET based on its therapeutic effect, while 14 patients selected it based on side effects. Most patients with progression after primary ET selected fulvestrant as the secondary ET based on its therapeutic and side effects. We await the final results from the HORSE-BC study.

Cost-effectiveness analysis of fulvestrant versus anastrozole as first-line treatment for hormone receptor-positive advanced breast cancer.

Although recent studies demonstrated that fulvestrant is superior to anastrozole as first-line treatment for hormone receptor (HR)-positive advanced breast cancer, the cost-effectiveness of fulvestrant versus anastrozole remained uncertain. Thus, the current study aimed to evaluate the cost-effectiveness of fulvestrant compared with anastrozole in the first-line setting. A Markov model consisting of three health states (stable, progressive and dead) was constructed to simulate a hypothetical cohort of patients with HR-positive advanced breast cancer. Costs were calculated from a Chinese societal perspective. Health outcomes were measured in quality-adjusted life-year (QALY). The incremental cost-effectiveness ratio (ICER) was expressed as incremental cost per QALY gained. Model results suggested that fulvestrant provides an additional effectiveness gain of 0.11 QALYs at an incremental cost of $32,654 compared with anastrozole, resulting in an ICER of $296,855/QALY exceeding the willingness-to-pay threshold of $23,700/QALY. Hence, fulvestrant is not a cost-effective strategy compared with anastrozole as first-line treatment for HR-positive advanced breast cancer.

Physician experiences and preferences in the treatment of HR+/HER2- metastatic breast cancer in the United States: a physician survey.

Sequential endocrine therapy (ET) is recommended for postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) and without visceral symptoms. Chemotherapy (CT) can be considered after sequential ETs, but is associated with adverse side effects. We assessed physicians' preferences and self-reported prescribing patterns for ET and CT in the treatment of HR+/HER2- mBC at community practices in the United States. Community-based oncologists/hematologists from a nationwide online panel who treated postmenopausal women with HR+/HER2- mBC were invited to complete a survey, blinded to the identity of study sponsor. Treatment preferences were collected by treatment class of ET-based regimens versus CT and by agent for postmenopausal HR+/HER2- mBC patients after prior nonsteroidal aromatase inhibitor use in the adjuvant or mBC setting. Among 213 physicians who completed the survey, 78% were male, 71% were based in small/intermediate practices (2-9 oncologists/subspecialists), 55% had >10 years of experience, and 58% referred to the National Comprehensive Cancer Network Guidelines when treating mBC. Among first-line ETs, anastrozole was the most frequently used treatment (35%), followed by everolimus-based (EVE, 34%) and fulvestrant-based (FUL, 15%) therapy. After first-line ET, the most preferred second- and third-line treatments were ET monotherapy (48% and 39%), ET combination therapy (31% and 19%), and CT monotherapy (13% and 30%). Comparing EVE versus FUL, physicians preferred EVE in all lines but first line. Efficacy was the most important consideration for treatment choice. Physicians prescribed CT in early lines mainly because of visceral symptoms. This survey of treatment patterns for HR+/HER2- mBC in community practice suggested that after first-line ET, ET mono- or combination therapy was commonly used for the second- and third-line treatments and CT monotherapy for third- or later line treatments. CTs were used in early lines for patients with visceral symptoms.