Enzalutamida y apalutamida en el tratamiento del cáncer de próstata no metastásico resistente a la castración: comparación indirecta de la eficacia

doi:10.1016/j.acuro.2019.03.007

Actas Urológicas Españolas

Volume 43, Issue 7, September 2019, Pages 355-363

https://doi.org/10.1016/j.acuro.2019.03.007 Get rights and content

Resumen

Objetivos

Realizar una comparación indirecta ajustada de la eficacia relativa de enzalutamida y apalutamida en pacientes con cáncer de próstata no metastásico resistente a la castración (CPRCnm) con alto riesgo de progresión a enfermedad metastásica.

Material y métodos

Tras realizar una búsqueda bibliográfica se llevó a cabo una comparación indirecta ajustada de la eficacia relativa de enzalutamida y apalutamida en pacientes con CPRCnm con alto riesgo de progresión a enfermedad metastásica siguiendo el método de Bucher et al. Como variables se seleccionaron la supervivencia libre de metástasis (SLM) y la tasa de respuesta al PSA (TRPSA).

Resultados

No se observaron diferencias estadísticamente significativas para las variables evaluadas entre enzalutamida y apalutamida. Para la comparación enzalutamida + TDA vs. apalutamida + TDA: SLM obtuvo un HR (IC95%) = 1,036 (0,781-1,373) y TRPSA obtuvo un RR (IC95%) = 0,81 (0,339-1,938).

Conclusiones

La comparación indirecta ajustada realizada en este estudio muestra que no existen diferencias estadísticamente significativas en términos de eficacia, a nivel de SLM y TRPSA, entre enzalutamida + TDA y apalutamida + TDA en pacientes con CPRCnm con alto riesgo de progresión a enfermedad metastásica. Sin embargo, se debería diseñar un ensayo independiente en el que se comparasen directamente ambos fármacos para confirmar estos resultados.

Abstract

Objectives

To perform an adjusted indirect comparison of the efficacy of enzalutamide and apalutamide in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) with a high risk of progression to metastatic disease.

Material and methods

After carrying out a literature search, we performed an adjusted indirect comparison (Bucher et al.) of the relative efficacy of enzalutamide and apalutamide in patients with nmCRPC with a high risk of progression to metastatic disease. The outcomes included were metastasis-free survival (MFS) and PSA response rate (PSARR).

Results

There were no statistically significant differences between enzalutamide and apalutamide regarding the analysed outcomes. For the comparison enzalutamide + ADT vs. apalutamide + ADT: MFS a HR (95% CI) = 1,036 (0.781-1.373) was obtained. For PSARR, a RR (95% CI) = 0.81 (0.339-1.938) was obtained.

Conclusions

The adjusted indirect comparison performed in this study shows that there are no statistically significant differences in terms of efficacy regarding MFS and PSARR between enzalutamide + ADT and apalutamide + ADT in patients with nmCRPC with a high risk of progression to metastatic disease. However, in order to confirm these results, an independent trial with direct comparison between both drugs would be required.

Section snippets

Introducción

El cáncer de próstata es, según la International Agency for Research on Cancer, la neoplasia con mayor incidencia y prevalencia en España (datos de 2012)¹. La tasa de incidencia estandarizada por edad es de 96,8 y la de mortalidad es de 15,2 por cada 100.000 habitantes/año1, 2. A nivel mundial hay 1.600.000 casos y 366.000 muertes anuales³.

Aproximadamente un tercio de los pacientes desarrollarán la enfermedad avanzada y finalmente todos terminarán desarrollando una enfermedad progresiva llamada

Objetivo

Realizar una comparación indirecta ajustada de la eficacia relativa de enzalutamida y apalutamida en pacientes con CPRCnm con alto riesgo de progresión a enfermedad metastásica.

Metodología

Para la identificación de los estudios relevantes publicados se llevó a cabo una búsqueda (25 octubre 2018) en las bases de datos Medline (a través de PubMed), The Cochrane Library y Centre for Reviews and Dissemination (CRD). Se utilizaron los términos libres: enzalutamide, apalutamide, prostate cancer y nonmetastatic prostate cancer. Se seleccionaron únicamente los artículos publicados en 2017 y 2018. También se hicieron búsquedas en las páginas web de la EMA, FDA y en las principales

Resultados

Se localizaron un total de 13 artículos y un informe de evaluación de tecnologías sanitarias.

Para la evaluación de enzalutamida, se localizaron 4 artículos en Medline: 3 artículos de revisión y un artículo que describía el ensayo PROSPER. Se seleccionó el ensayo pivotal PROSPER¹⁵, que fue el único ensayo que coincidía con la pregunta PICO(D). Los demás artículos hacían referencia a este ensayo de un modo narrativo.

Para la evaluación de apalutamida, se localizaron: el ensayo pivotal SPARTAN¹⁶, 8

Discusión

La necesidad de posicionar fármacos que a priori se presentan como alternativas para una misma indicación y población es inherente a los sistemas públicos de salud dado que los recursos son limitados y estos deben garantizar los mejores resultados en salud de la forma más eficiente.

En un escenario ideal, los datos con mayor nivel de evidencia para realizar dicho posicionamiento serían los provenientes de un ECA en el que se compararan directamente los 2 fármacos destinados al mismo objetivo

Conclusiones

Sin embargo, se debería diseñar un ensayo independiente en el que se comparasen directamente ambos fármacos para confirmar estos resultados.

Conflicto de intereses

Los autores declaran no tener ningún conflicto de intereses.

Bibliografía (22)

J. Ferlay et al.
Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012
Eur J Cancer.
(2013)
M.S. Cookson et al.
Castration-resistant prostate cancer: AUA Guideline
J Urol.
(2013)
J. Mateo et al.
Managing nonmetastatic castration-resistant prostate cancer
Eur Urol.
(2019)
H.C. Bucher et al.
The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials
J Clin Epidemiol.
(1997)
J. Ferlay et al.
Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012
Int J Cancer
(2015)
C. Fitzmaurice et al.
Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the Global Burden of Disease Study
JAMA Oncol.
(2017)
NCCN (Clinical Practice Guidelines in Oncology (NCCN Guidelines) Prostate Cancer. Version 4.2018 [Internet]. Fort...
M.R. Smith et al.
Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer
J Clin Oncol.
(2005)
M.R. Smith et al.
Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration-resistant nonmetastatic prostate cancer
Cancer.
(2011)
European Medicine Agency (EMA). Summary of opinion (post authorisation) for Xtandi® [Internet]. Londres: EMA;...

European Medicine Agency (EMA). Summary of opinion (post authorisation) for Erleada® [Internet]. Londres: EMA;...

Cited by (6)

Comparative efficacy of apalutamide darolutamide and enzalutamide for treatment of non-metastatic castrate-resistant prostate cancer: A systematic review and network meta-analysis
2020, Urologic Oncology: Seminars and Original Investigations
Citation Excerpt :
Moreover, all studies have followed patients every 16 weeks with imaging studies for assessment of new metastatic lesions. Similar to our findings, prior studies could not find a difference in MFS between apalutamide and enzalutamide in multiple indirect comparisons [13,20]. However, difference between apalutamide and enzalutamide, and darolutamide is statistically significant.
Introduction: Studies using apalutamide, enzalutamide, or darolutamide have shown improved metastasis free survival (MFS) rates, leaving clinicians with a dilemma of choosing one over the other, for nonmetastatic castration recurrent prostate cancer (nmCRPC). We performed a network meta-analysis to provide an indirect comparison of oncologic outcomes and adverse events (AEs) of these medications. Material and Methods: We searched PubMed, MEDLINE, and SCOPUS databases, for studies reporting apalutamide, enzalutamide, or darolutamide until January 25, 2020. Results were input into an EndNote library, and data were extracted into a predefined template. Progression free survival (PFS) was defined as radiologic progression or death. Network meta-analysis was done using R and meta-analysis was performed with RevMan v. 5. Surface under the cumulative ranking (SUCRA) value was used to provide rank probabilities. Results: We found 3 studies reporting results for apalutamide, enzalutamide, and darolutamide. MFS was significantly lower in patients receiving darolutamide compared to both apalutamide (hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.55–0.97) and enzalutamide (HR: 0.71, 95% CI: 0.54–0.93). MFS was similar for enzalutamide and apalutamide (HR: 0.97, 95% CI: 0.73–1.28). In PFS, apalutamide showed a slightly higher rate compared to darolutamide (HR: 0.76, 95% CI: 0.59–0.99). There was no difference in overall survival (OS) between any of the medications. There was no statistically significant difference in AEs profile of the 3 medications. However, darolutamide had the highest SUCRA value and probability of being the most preferred medication based on AEs profile. Conclusion: Enzalutamide and apalutamide had similar and higher MFS rate in indirect comparison with darolutamide. In cases where AEs are concerning, darolutamide might be the preferred agent.
Apalutamide compared with darolutamide for the treatment of non-metastatic castration resistant prostate cancer: efficacy and tolerability in a matching-adjusted indirect comparison
2022, Onkourologiya
Apalutamide Compared with Darolutamide for the Treatment of Non-metastatic Castration-Resistant Prostate Cancer: Efficacy and Tolerability in a Matching-Adjusted Indirect Comparison
2022, Advances in Therapy
Pharmacotherapeutic strategies for castrate-resistant prostate cancer
2020, Expert Opinion on Pharmacotherapy
Matching-Adjusted Indirect Comparison of Health-Related Quality of Life and Adverse Events of Apalutamide Versus Enzalutamide in Non-Metastatic Castration-Resistant Prostate Cancer
2020, Advances in Therapy
Apalutamide: A new agent in the management of prostate cancer
2019, Journal of Oncology Pharmacy Practice

View full text

Resumen

Objetivos

Material y métodos

Resultados

Conclusiones

Abstract

Objectives

Material and methods

Results

Conclusions

Section snippets

Introducción

Objetivo

Metodología

Resultados

Discusión

Conclusiones

Conflicto de intereses

Eur J Cancer.

J Urol.

Eur Urol.

J Clin Epidemiol.

Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012

Int J Cancer

Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the Global Burden of Disease Study

JAMA Oncol.

Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer

J Clin Oncol.

Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration-resistant nonmetastatic prostate cancer

Cancer.