[Cost-effectiveness analysis of aflibercept in combination with FOLFIRI in the treatment of patients with metastatic colorectal cancer]. / Análisis coste-efectividad de aflibercept en combinación con FOLFIRI en el tratamiento de pacientes con cáncer colorrectal metastásico.

OBJECTIVES: To estimate the incremental cost per life-year gained (LYG) of aflibercept in combination with FOLFIRI as second-line treatment in metastatic colorectal cancer (mCRC) patients previously treated with oxaliplatin. METHODS: Based on clinical trial VELOUR results, a three-state Markov model (stable disease, progression and death) with 2-week cycle duration was designed. Transition to health state «progression¼ implied the interruption of second-line treatment and administration of a third-line treatment (post-second line chemotherapy). Cost estimation included disease management cost (pharmaceutical, adverse event management, administration costs, etc.). Both cost and outcomes were discounted (3% annually). Sensitivity analyses (SA) were performed to test model robustness. RESULTS: Administration of aflibercept + FOLFIRI as second-line treatment provided 1.78 LYG (21 life-months gained). With FOLFIRI 1.43 LYG (17 months) were obtained. The cost of the clinical management of aflibercept + FOLFIRI implied an additional investment of Euros 13,564 compared with FOLFIRI for a lifetime horizon, being total costs for aflibercept + FOLFIRI of Euros 38,346, compared to Euros 24,782 with FOLFIRI. In the cost-effectiveness analysis Euros 38,931/LYG was obtained with aflibercept in combination with FOLFIRI versus FOLFIRI. CONCLUSION: Aflibercept in combination with FOLFIRI increased overall survival versus FOLFIRI, so it is an effective strategy in the treatment of patients with mCRC. Aflibercept in combination with FOLFIRI is an efficient strategy for second-line mCRC treatment from the National Health System perspective.

OBJETIVOS: Estimar el coste incremental por año de vida ganado (AVG) de la utilización de aflibercept en combinación con FOLFIRI como tratamiento de 2ª línea en pacientes con cáncer colorrectal metastásico (CCRm) previamente tratados con oxaliplatino. MATERIAL Y MÉTODOS: Basándose en los resultados del ensayo clínico VELOUR, se utilizó un modelo de Markov con 3 estados de salud (enfermedad estable, progresión y muerte) y ciclos de 2 semanas. La transición al estado de salud «progresión¼ implicaba interrumpir el tratamiento en 2ª línea y administrar una 3ª línea de tratamiento. La estimación de costes incluyó costes del manejo de la enfermedad (farmacológicos, acontecimientos adversos, administración, etc.). Costes y resultados en salud fueron descontados al 3% anualmente. Para probar la robustez del modelo se realizaron análisis de sensibilidad determinístico y probabilístico. RESULTADOS: La administración de aflibercept + FOLFIRI como 2ª línea de quimioterapia aporta 1,78 AVG (21 meses de vida ganados). Con FOLFIRI se consiguen 1,43 AVG (17 meses). El coste del manejo clínico de aflibercept + FOLFIRI supone una inversión adicional de 13.564 frente a FOLFIRI a lo largo de toda la vida del paciente, siendo el coste total de 38.346 para aflibercept + FOLFIRI y 24.782 para FOLFIRI. Se obtiene un RCEI (ratio coste efectividad incremental) de 38.931 /AVG con aflibercept + FOLFIRI frente a FOLFIRI. CONCLUSIÓN: Aflibercept en combinación con FOLFIRI incrementa la supervivencia global frente a FOLFIRI, lo que supone una estrategia efectiva en el tratamiento de pacientes con CCRm. La relación coste-efectividad incremental de aflibercept en combinación con FOLFIRI supone una estrategia eficiente, coste-efectiva, para el Sistema Nacional de Salud.

Assessing health-state utility values in patients with metastatic colorectal cancer: a utility study in the United Kingdom and the Netherlands.

PURPOSE: This study aimed to elicit EuroQol Quality of Life 5-Dimensions (EQ-5D) utility values from patients with second-line metastatic colorectal cancer (mCRC) pre- and post-progression. METHODS: A cross-sectional study was conducted in five hospitals in the Netherlands and the UK. Patients with mCRC were eligible if prescribed a second or subsequent line of therapy or best supportive care (BSC), received prior oxaliplatin in first-line therapy, and had Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-2 at second-line initiation. Patients completed the EuroQol Quality of Life 5-Dimensions 3-levels (EQ-5D-3L) questionnaire and were categorized as pre- or post-progression. Chart data including patient demographics, clinical history, prior/current treatments and serious adverse events (SAEs) were collected. Mean utilities were estimated; uni- and multivariate analyses were conducted. RESULTS: Seventy-five patients were enrolled; 42 were pre-progression defined as second line or third line following an AE on second line and 33 were post-progression defined as third or subsequent therapy lines or BSC. Patient/disease characteristics and number of SAEs were similar between cohorts. Mean utility scores were 0.741 (SD = 0.230) and 0.731 (SD = 0.292) for pre- and post-progression cohorts, respectively. Compared to pre-progression, more patients reported increased anxiety/depression (36 vs. 12 %) and fewer problems with daily activities (64 vs. 38 %) post-progression. More patients pre-progression were on active treatment at enrolment (83 vs. 42 %) compared to post-progression. CONCLUSIONS: This is the first real-world study to collect utilities for patients with second-line mCRC pre- and post-disease progression. Utility values were similar pre- and post-progression. To further explore the effect of radiological progression on utilities, longitudinal research is required that includes patients in palliative care centres.

Análisis coste-efectividad de aflibercept en combinación con FOLFIRI en el tratamiento de pacientes con cáncer colorrectal metastásico / Cost-effectiveness analysis of aflibercept in combination with FOLFIRI in the treatment of patients with metastatic colorectal cancer

Objetivos: Estimar el coste incremental por año de vida ganado (AVG) dela utilización de aflibercept en combinación con FOLFIRI como tratamiento de 2ª línea en pacientes con cáncer color rectal metastásico (CCRm) previamente tratados con oxaliplatino. Material y métodos: Basándose en los resultados del ensayo clínico VELOUR, se utilizó un modelo de Markov con 3 estados de salud (enfermedad estable, progresión y muerte) y ciclos de 2 semanas. La transición al estado de salud «progresión» implicaba interrumpir el tratamiento en 2ªlínea y administrar una 3ª línea de tratamiento. La estimación de costes incluyó costes del manejo de la enfermedad (farmacológicos, acontecimientos adversos, administración, etc.). Costes y resultados en salud fueron descontados al 3% anualmente. Para probar la robustez del modelo se realizaron análisis de sensibilidad determinístico y probabilístico. Resultados: La administración de aflibercept + FOLFIRI como 2ª línea de quimioterapia aporta 1,78 AVG (21 meses de vida ganados). Con FOLFIRI se consiguen 1,43 AVG (17 meses). El coste del manejo clínico de aflibercept + FOLFIRI supone una inversión adicional de 13.564 Euros frente a FOLFIRI a lo largo de toda la vida del paciente, siendo el coste total de 38.346 Euros para aflibercept + FOLFIRI y 24.782 Euros para FOLFIRI. Se obtiene un RCEI (ratio coste efectividad incremental) de 38.931 Euros/AVG con aflibercept + FOLFIRI frente a FOLFIRI. Conclusión: Aflibercept en combinación con FOLFIRI incrementa la supervivencia global frente a FOLFIRI, lo que supone una estrategia efectiva en el tratamiento de pacientes con CCRm. La relación coste-efectividad incremental de aflibercept en combinación con FOLFIRI supone una estrategia eficiente, coste-efectiva, para el Sistema Nacional de Salud (AU)

Objectives: To estimate the incremental cost per life-year gained (LYG) of aflibercept in combination with FOLFIRI as second-line treatment inmetastatic colorectal cancer (mCRC) patients previously treated with oxaliplatin. Methods: Based on clinical trial VELOUR results, a three-state Markovmodel (stable disease, progression and death) with 2-week cycle duration was designed. Transition to health state «progression» implied the interruption of second-line treatment and administration of a third-line treatment(post-second line chemotherapy). Cost estimation included disease management cost (pharmaceutical, adverse event management, administration costs, etc.). Both cost and outcomes were discounted (3% annually).Sensitivity analyses (SA) were performed to test model robustness. Results: Administration of aflibercept + FOLFIRI as second-line treatment provided 1.78 LYG (21 life-months gained). With FOLFIRI 1.43 LYG (17months) were obtained. The cost of the clinical management of aflibercept+ FOLFIRI implied an additional investment of Euros 13,564 compared with FOLFIRI for a lifetime horizon, being total costs for aflibercept + FOLFIRI of Euros 38,346, compared to Euros 24,782 with FOLFIRI. In the cost-effectiveness analysis Euros 38,931/LYG was obtained with aflibercept in combination with FOLFIRI versus FOLFIRI. Conclusion: Aflibercept in combination with FOLFIRI increased overall survival versus FOLFIRI, so it is an effective strategy in the treatment of patients with mCRC. Aflibercept in combination with FOLFIRI is an efficient strategy for second-line mCRC treatment from the National Health System perspective (AU)

Mean overall survival gain with aflibercept plus FOLFIRI vs placebo plus FOLFIRI in patients with previously treated metastatic colorectal cancer.

BACKGROUND: Mean survival in cancer trials can be estimated with statistical techniques to extrapolate study survival curves. This methodology was applied to data from the VELOUR trial, where use of the novel biologic aflibercept (ziv-aflibercept in the United States) in combination with fluorouracil+leucovorin+irinotecan (FOLFIRI), had significantly increased median overall survival (OS) by 1.44 months, vs placebo plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) resistant to, or that had progressed following, an oxaliplatin-containing regimen. METHODS: Parametric survival analyses were used to identify distributions with the best fit to the empirical VELOUR data. Mean OS for the two treatment groups (and pre-defined subgroups) was calculated from the fitted curves over a 15-year survival period. RESULTS: Overall, the log-logistic distribution was the best-fitting for both treatment arms and, with it, the estimated difference in mean OS over 15 years between aflibercept+FOLFIRI and placebo+FOLFIRI was 4.7 months. In addition, the survival advantage with aflibercept was at least 3 months for the ITT population, whichever distribution was used to extrapolate survival. CONCLUSION: Extrapolation of survival curves suggests the mean OS difference for aflibercept in the VELOUR trial is at least 3 months in the ITT population and selected subgroups.