Ana Lluch Hospital Clínico Universitario Valencia

Ana Lluch Hospital Clínico Universitario Valencia
¿Impacta la aparición de una Metástasis Ósea en la Calidad de Vida del Paciente con Cáncer? Ana Lluch Hospital Clínico Universitario Valencia

Incidencia de metástasis óseas (%, intervalo)
Las Metástasis Óseas son frecuentes en los pacientes con Cánceres Avanzados Incidencia de metástasis óseas (%, intervalo) 20-25% 14-45% 40% 60% 30-40% 65-75% Bone metastases affect a large proportion of patients with advanced cancer, in particular those with breast, prostate, thyroid, lung or bladder cancer.1 This slide shows the percentage of patients with bone metastases recorded at post-mortem examination.1 The incidence of bone metastases is particularly high in patients with breast cancer (range 65−75%), prostate cancer (range 65−75%), thyroid cancer (60%), lung cancer (range 30−40%) and bladder cancer (40%).1 Reference Coleman RE. Bone metastases. Metastatic bone: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 2001;27:165–76. Renal Melanoma Vejiga Supervivencia global Tiroides Pulmón Mama Próstata Coleman RE. Cancer Treat Rev 2001;27:165–76.

CONSECUENCIAS DE LAS METASTASIS OSEAS: Squeletal-related events (ERE)
PERDIDA DE ATONOMIA DOLOR INCREMENTO DE COSTO SANITARIO COMPRESION MEDULAR METASTASIS OSEAS CIRUGIA HIPERCALCEMIA RADIOTERAPIA FRACTURAS REDUCCION DE SUPERVIVENCIA

Compresión de la médula espinal
DMO-IHQ-AMG Las Metástasis Óseas pueden producir acontecimientos severos para el esqueleto (EREs) Desde finales de los 90, los ERE han sido definidos como:1,2 La eficacia de los agentes diana para hueso en el tratamiento de las metástasis óseas se evalua mediante el uso de un criterio de ERE2 Radioterapia ósea Fractura patológica Compresión de la médula espinal Cirugía ósea References Saad F, Gleason DM, Murray R et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 2004;96:879–2. (Accessed 2 March 2011). Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 2006;12:6243s–9s. Chow E, Harris K, Fan G et al. Palliative radiotherapy trials for bone metastases: a systematic review. J Clin Oncol 2007;25:1423–36. Lipton A, Theriault RL, Hortobagyi GN et al. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials. Cancer 2000;88:1082–90. Delea T, McKiernan J, Brandman J et al. Retrospective study of the effect of skeletal complications on total medical care costs in patients with bone metastases of breast cancer seen in typical clinical practice. J Support Oncol 2006;4:341–7. 1. Saad F et al. J Natl Cancer Inst 2004;96:879–82; 2. (Accessed 2 March 2011).

Complicaciones concomitantes a los EREs
Complicaciones potenciales Fractura Patológica Aumento del tiempo de curación Supervivencia reducida1,2 Pérdida de movilidad Necesidad de atención y cuidados de enfermería en domicilio Radiación ósea Posibilidad de “dolor agudo” tras el tto Mielosupresión5 Visitas frecuentes para tratar la compresión en la médula espinal6 References Gainor BJ, Buchert P. Fracture healing in metastatic bone disease. Clin Orthopaed Rel Res 1983;178:297–302. Saad F, Lipton A, Cook R et al. Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer 2007;110:1860–7. Poor G, Atkinson EJ, Lewallen DG et al. Age-related hip fractures in men: clinical spectrum and short-term outcomes. Osteoporos Int 1995;5:419–26. Loblaw DA, Wu JS, Kirkbride P et al. Pain flare in patients with bone metastases after palliative radiotherapy--a nested randomized control trial. Supp Care Cancer 2007;15:451–5. Hellman RS, Krasnow AZ. Radionuclide therapy for palliation of pain due to osteoblastic metastases. J Palliat Med 1998;1:277–83. Maranzano E, Trippa F, Chirico L et al. Management of metastatic spinal cord compression Tumori 2003;89:469–75. Katzer A, Meenen NM, Grabbe F et al. Surgery of skeletal metastases. Arch Orthopaed Trauma Surg 2002;122:251–8. Loblaw DA, Perry J, Chambers A et al. Systematic review of the diagnosis and management of malignant extradural spinal cord compression: the Cancer Care Ontario Practice Guidelines Initiative's Neuro-Oncology Disease Site Group. J Clin Oncol 2005;23:2028–3. SRE: skeletal related event, 1. Gainor, Buchert. Clin Orthopaed Rel Res 1983;178:297–302; 2. Saad F et al. Cancer 2007;110:1860–7; 3. Poor et al. Osteoporos Int 1995;5:419–26; 4. Loblaw et al. Supp Care Cancer 2007;15:451–5; 5. Hellman, Krasnow. J Palliat Med 1998;1:277–83; 6. Maranzano et al. Tumori 2003;89:469–75; 7. Katzer et al. Arch Orthopaed Trauma Surg 2002;122:251–8; 8. Loblaw et al. J Clin Oncol 2005;23:2028–3. 5

Complicaciones concomitantes a los EREs
Complicaciones potenciales Cirugía de hueso Estancia hospitalaria Tasa de mortalidad de un 8% (aprox.) durante el ingreso7 Tasa elevada de complicaciones quirúrgicas7,8 Tasa elevada de fracaso; imposibilidad para recuperar las funciones7 Compresión de la médula espinal Dolor intenso8 Necesidad de tratamiento con esteroides8 Visitas frecuentes a Radioterapia6 Paraplejia o parestesias irreversibles8 Incontinencia8 References Gainor BJ, Buchert P. Fracture healing in metastatic bone disease. Clin Orthopaed Rel Res 1983;178:297–302. Saad F, Lipton A, Cook R et al. Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer 2007;110:1860–7. Poor G, Atkinson EJ, Lewallen DG et al. Age-related hip fractures in men: clinical spectrum and short-term outcomes. Osteoporos Int 1995;5:419–26. Loblaw DA, Wu JS, Kirkbride P et al. Pain flare in patients with bone metastases after palliative radiotherapy--a nested randomized control trial. Supp Care Cancer 2007;15:451–5. Hellman RS, Krasnow AZ. Radionuclide therapy for palliation of pain due to osteoblastic metastases. J Palliat Med 1998;1:277–83. Maranzano E, Trippa F, Chirico L et al. Management of metastatic spinal cord compression Tumori 2003;89:469–75. Katzer A, Meenen NM, Grabbe F et al. Surgery of skeletal metastases. Arch Orthopaed Trauma Surg 2002;122:251–8. Loblaw DA, Perry J, Chambers A et al. Systematic review of the diagnosis and management of malignant extradural spinal cord compression: the Cancer Care Ontario Practice Guidelines Initiative's Neuro-Oncology Disease Site Group. J Clin Oncol 2005;23:2028–3. SRE: skeletal related event, 1. Gainor, Buchert. Clin Orthopaed Rel Res 1983;178:297–302; 2. Saad F et al. Cancer 2007;110:1860–7; 3. Poor et al. Osteoporos Int 1995;5:419–26; 4. Loblaw et al. Supp Care Cancer 2007;15:451–5; 5. Hellman, Krasnow. J Palliat Med 1998;1:277–83; 6. Maranzano et al. Tumori 2003;89:469–75; 7. Katzer et al. Arch Orthopaed Trauma Surg 2002;122:251–8; 8. Loblaw et al. J Clin Oncol 2005;23:2028–3. 6

LAS FRACTURAS TIENEN UN IMPACTO NEGATIVO EN LA SUPERVIVENCIA

Los pacientes con metástasis óseas y ERE tienen un peor pronóstico que los pacientes sin ERE
Curvas de supervivencia de pacientes con cáncer de mama con metástasis óseas (n = 2.216) con y sin ERE Supervivencia mediana, meses 1 0,9 0,8 0,7 0,6 0,4 0,3 0,2 0,1 2 3 4 5 6 7 8 9 10 Metástasis óseas sin ERE 16 Metástasis óseas con ERE 7 Proporción que sobreviven Tiempo transcurrido tras el diagnóstico de metástasis ósea (años) Patients with bone metastases and SREs have poorer survival than those without SREs.1−4 This slide shows data from a population-based cohort study of 35,912 newly diagnosed breast cancer patients conducted in Denmark (1999−2007).1 Among patients with bone metastases (n = 2216), median survival was 16 months for those without SREs and 7 months for those with both bone metastases and SREs.1 5-year survival was 75.8% for breast cancer patients without bone metastases, falling substantially to 8.3% for patients with bone metastases and to 2.5% for those with both bone metastases and SREs.1 An association between SREs and poor prognosis has also been reported in patients with lung cancer,2 prostate cancer3 and in another large population-based cohort analysis in patients with breast cancer.4 References Yong M, Jensen AÖ, Jacobsen JB, et al. Survival in breast cancer patients with bone metastases and skeletal-related events: a population-based cohort study in Denmark ( ). Breast Cancer Res Treat 2011;129:495−503. Tsuya A, Kuratab T, Tamurac K, et al. Skeletal metastases in non-small cell lung cancer: a retrospective study. Lung Cancer 2007;57:229−32. De Puy V, Anstrom KJ, Castel LD, et al. Effects of skeletal morbidities on longitudinal patient-reported outcomes and survival in patients with metastatic prostate cancer. Support Care Cancer 2007;15:869–76. Sathiakumar N, Delzell E, Morrisey MA, et al. Mortality following bone metastasis and skeletal-related events among women with breast cancer: a population-based analysis of U.S. Medicare beneficiaries, 1999–2006. Breast Cancer Res Treat 2012;131:231−8. Yong M, et al. Breast Cancer Res Treat 2011;129:495−503. Los datos proceden de un estudio de cohortes basado en una población de pacientes con cáncer de mama recién identificadas realizado en Dinamarca ( ).

Incidencia acumulada de ERE durante el estudio
Los ERE son una complicación habitual en pacientes con tumores sólidos y metástasis óseas Incidencia acumulada de ERE durante el estudio en pacientes con metástasis óseas recién diagnosticadas 1 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 6 12 18 24 30 36 Mes del estudio Incidencia acumulada de ERE durante el estudio Cáncer de mama (n = 621) Cáncer de pulmón (n = 477) Cáncer de próstata (n = 721) SREs are a common complication in patients with solid tumours and bone metastases.1 A review of medical records from two large US health systems was conducted to assess the risk of SREs (spinal cord compression, pathological fracture, radiation to bone, bone surgery) in patients with solid tumours (breast cancer: n = 621; lung cancer: n = 477; prostate cancer: n = 721) in routine clinical practice.1 Cumulative incidence of SREs in patients with newly diagnosed bone metastases was estimated, accounting for death as a competing risk.1 Intravenous (IV) bisphosphonates were received by 55.8%, 14.8% and 20.2% of patients with breast cancer, lung cancer and prostate cancer, respectively.1 More than one half of patients with bone metastases had evidence of SREs (breast cancer: 62.6%; lung cancer: 58.7%; prostate cancer: 51.7%) either at diagnosis of bone metastases or subsequently.1 Reference Oster G, Lamerato L, Glass AG, et al. Natural history of skeletal-related events in patients with breast, lung, or prostate cancer and metastases to bone: a 15-year study in two large US health systems. Support Care Cancer 2013;21:327986. Uso de bisfosfonatos intravenosos: cáncer de mama, 55,8%; cáncer de pulmón, 14,8%; y cáncer de próstata, 20,2%. Oster G, et al. Support Care Cancer 2013;21:327986.

Los ERE previos aumentan el riesgo de ERE posteriores
Cáncer de mama1 Cáncer de próstata2 Cáncer de pulmón y otros tumores sólidos3 % de pacientes con ERE durante el estudio Key Point Data from breast, prostate, and lung cancer studies show that patients who had prior SREs are at greater risk for subsequent SREs. Background Kaminski et al retrospectively analysed data from a previous report on the long-term efficacy of IV bisphosphonate therapy in the treatment of skeletal complications in patients (N = 1648) with advanced breast cancer or multiple myeloma.1,4 Patients were stratified based on whether they had an SRE before study entry1 Before study entry, 760 patients (68%) had experienced at least one SRE1 These patients had a 2-fold higher risk of developing an SRE on study than patients with no SRE (hazard ratio [HR] = 2.0)1 Across treatment groups, ~58% of these patients had at least one SRE on study vs only 32% of patients with no SRE before study entry1 Saad et al retrospectively analyzed data on the continued efficacy of IV bisphosphonate therapy during long-term treatment (N = 422) in patients with advanced prostate cancer and bone metastases; patients were stratified based on SRE history.2 Before study entry, 144 patients (34%) had experienced at least one SRE2 These patients had a higher probability of experiencing an on-study SRE than patients with no previous SRE (odds ratio [OR] = 1.23)2 In the placebo group, 51% of patients with prior SREs had a least one SRE on study vs 47% of patients with no SRE before study entry2 Hirsh et al retrospectively analysed data from a trial of IV bisphosphonate therapy in patients with bone metastases secondary to lung cancer or other solid tumors; patients were stratified based on SRE history.3 Before study entry, 347 patients (69%) had experienced at least one SRE3 These patients had a 1.4-fold increased risk of experiencing an on-study SRE compared with patients with no prior SRE (OR = 1.41; P = 0.036)3 In the placebo group, 52% of patients with prior SRE had at least one SRE on study vs 40% of patients with no SRE before study entry3 References Kaminski M, Rosen L, Gordon D, et al. Zoledronic acid versus pamidronate in patients with breast cancer and multiple myeloma who are at high risk for skeletal complications. Poster presented at: American Society of Clinical Oncology Annual Meeting. June 5-8, 2004; New Orleans, Louisiana. Abstract 857. Saad F, Chen YM, Gleason DM, Chin J. Continuing benefit of zoledronic acid in preventing skeletal complications in patients with bone metastases. Clin Genitourin Cancer. 2007;5:3906. Hirsh V, Tchekmedyian NS, Rosen LS, Zheng M, Hei YJ. Clinical benefit of zoledronic acid in patients with lung cancer and other solid tumors: analysis based on history of skeletal complications. Clin Lung Cancer 2004;6:1704. ERE previos Sin ERE previos ERE: evento relacionado con el esqueleto. 1. Kaminski M, et al. Póster presentado en la reunión anual de la ASCO. 5-8 de junio de 2004; Nueva Orleans; LA. Resumen 857; 2. Saad F, et al. Clin Genitourin Cancer 2007;5:3906; 3. Hirsh V, et al. Clin Lung Cancer 2004;6:1704. 10

Los ERE suponen una carga considerable para los pacientes y los sistemas sanitarios
Conse cuenci as directa s para los pacie ntes Fractura patológica1 Compresión de la médula espinal1 Cirugía ósea1 Radioterapia ósea para el dolor óseo1 Conse cuenci as indirec tas para los pacient es Peor estado físico, funcional y emocional2 Reducción de la HRQoL2 Visitas/estancias hospitalarias3 SREs are a substantial burden to patients and healthcare systems. Direct consequences to patients include: the need for radiation to bone for bone pain; pathological fracture; spinal cord compression; and surgery to bone.1 Additional, indirect consequences to patients include negative effects on physical, functional and emotional status,2 the requirement to undergo hospital visits and stays,3 and an overall reduction in HRQoL.2 SREs are also associated with substantial healthcare resource utilisation due to higher treatment costs vs advanced cancer without SREs4 and the need for hospital visits and inpatient stays.3 References Costa L and Major PP. Effect of bisphosphonates on pain and quality of life in patients with bone metastases. Nat Clin Prac Oncol 2009;6:163–74. De Puy V, Anstrom KJ, Castel LD, et al. Effects of skeletal morbidities on longitudinal patient-reported outcomes and survival in patients with metastatic prostate cancer. Supp Cancer Care 2007;15:869–76. Pocket RD, Castellano D, McEwan P, et al. The hospital burden of disease associated with bone metastases and skeletal-related events in patients with breast cancer, lung cancer, or prostate cancer in Spain. Eur J Cancer Care 2010;19:755–60. Delea T, McKiernan J, Brandman J, et al. Retrospective study of the effect of skeletal complications on total medical care costs in patients with bone metastases of breast cancer seen in typical clinical practice. J Support Oncol 2006;4:341–7. Impacto en los pacientes y los sistemas sanitarios HRQoL: calidad de vida relacionada con la salud.

Uso de rec urs os san itari os
Los ERE suponen una carga considerable para los pacientes y los sistemas sanitarios Uso de rec urs os san itari os Aumento de los costes de tratamiento4 Aumento de las visitas/estancias hospitalarias3 SREs are a substantial burden to patients and healthcare systems. Direct consequences to patients include: the need for radiation to bone for bone pain; pathological fracture; spinal cord compression; and surgery to bone.1 Additional, indirect consequences to patients include negative effects on physical, functional and emotional status,2 the requirement to undergo hospital visits and stays,3 and an overall reduction in HRQoL.2 SREs are also associated with substantial healthcare resource utilisation due to higher treatment costs vs advanced cancer without SREs4 and the need for hospital visits and inpatient stays.3 References Costa L and Major PP. Effect of bisphosphonates on pain and quality of life in patients with bone metastases. Nat Clin Prac Oncol 2009;6:163–74. De Puy V, Anstrom KJ, Castel LD, et al. Effects of skeletal morbidities on longitudinal patient-reported outcomes and survival in patients with metastatic prostate cancer. Supp Cancer Care 2007;15:869–76. Pocket RD, Castellano D, McEwan P, et al. The hospital burden of disease associated with bone metastases and skeletal-related events in patients with breast cancer, lung cancer, or prostate cancer in Spain. Eur J Cancer Care 2010;19:755–60. Delea T, McKiernan J, Brandman J, et al. Retrospective study of the effect of skeletal complications on total medical care costs in patients with bone metastases of breast cancer seen in typical clinical practice. J Support Oncol 2006;4:341–7. Impacto en los pacientes y los sistemas sanitarios HRQoL: calidad de vida relacionada con la salud.

Las metástasis óseas son la causa más frecuente de dolor en los pacientes con cáncer avanzado
Mediadores químicos Aumento de la presión del hueso Microfracturas Estiramiento del periostio Espasmo muscular reactivo Infiltración en la raíz del nervio Compresión del nervio Metástasis óseas Dolor óseo Bone metastases are the most common cause of advanced cancer-related pain. Possible mechanisms of pain due to bone metastases include the release of chemical mediators, increased pressure within the bone, microfractures, stretching of the bone periosteum, reactive muscle spasm, nerve root infiltration and compression of nerves by the collapse of vertebrae.1 Reference Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997;69:1−18. Mercadante S. Pain 1997;69:1−18.

El dolor óseo reduce la independencia funcional y la calidad de vida del paciente
CRÓNICO Dolor continuo, sordo, penetrante o pulsátil. La gravedad aumenta con la progresión de la enfermedad. AGUDO Dolor intercurrente o dolor incidental (ERE). Aparece espontáneamente o cuando soporta peso un hueso afectado. Bone pain can be categorised as either chronic (continuous dull, aching or throbbing pain) or acute (sudden ‘breakthrough’ or incident pain). Chronic pain tends to increase in severity with disease progression whereas acute pain occurs spontaneously or when weight is put on an affected bone.1 The consequences of bone pain can include reduced functional independence and HRQoL.2 References Sabino MA and Mantyh PW. Pathophysiology of bone cancer pain. J Support Oncol 2005;3:15−24. Lipton A. Treatment of bone metastases and bone pain with bisphosphonates. Support Cancer Ther 2007;4:92−100. Reducción de la independencia funcional y la calidad de vida Sabino MA y Mantyh PW. J Support Oncol 2005;3:15−24; Lipton A. Support Cancer Ther 2007;4:92−100.

La mayoría de los pacientes con metástasis óseas presentan dolor
Característica1 Proporción de pacientes (%)† (N = 5.544) Intensidad del dolor Sin dolor 15,5 Dolor leve 36,1 Dolor moderado 21,9 Dolor intenso 26,5 Uso de analgésicos Sin uso de analgésicos 47,8 Uso de analgésicos basados en opioides 35,0 Data from 5544 patients with bone metastases from solid tumours enrolled in three Phase III trials of denosumab vs zoledronic acid show that the majority were experiencing some degree of pain at baseline; furthermore, more than a quarter were experiencing severe pain.1 Typically, however, bone pain is not adequately managed.2 In this sample, almost one half of patients were not receiving any analgesia at the start of the study.2 References von Moos R, Body J-J, Egerdie B, et al. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer 2013;21:3497−507. Lipton A. Treatment of bone metastases and bone pain with bisphosphonates. Support Cancer Ther 2007;4:92−100. Es habitual que el dolor óseo no se trate adecuadamente.2 1. von Moos R, et al. Support Care Cancer 2013;21:3497507; 2. Lipton A. Support Cancer Ther 2007;4:92−100. †Los datos son datos basales agrupados por pacientes en los tres estudios pivotales de fase III de prevención de ERE con denosumab. El análisis excluye a los pacientes con mieloma múltiple.

Los ERE se asocian a una reducción de la HRQoL
Radioterapia ósea Fractura patológica Otros ERE -0,1 -0,2 -0,3 Cambio en la FACT-G (tamaño del efecto estandarizado†) -0,4 -0,5 Total Físico Funcional Emocional SREs due to bone metastases are associated with reduced HRQoL.1 The slide shows data from 248 men with metastatic castration-resistant prostate cancer (CRPC) who experienced an SRE during a placebo-controlled study of zoledronic acid. HRQoL was assessed using a questionnaire called the Functional Assessment of Cancer Therapy-General (FACT-G), where a negative change in FACT-G score represents a reduction in HRQoL.1 All types of SRE were associated with a reduction in HRQoL, including physical, functional and emotional components.1 Reference Weinfurt KP, Li Y, Castel LD, et al. The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol 2005;16:579–84. -0,6 -0,7 †Cálculo realizado dividiendo el cambio medio ajustado por la desviación estándar basal de toda la muestra del ensayo. Datos procedentes de 248 hombres con cáncer de próstata resistente a la castración y metástasis óseas que experimentaron un ERE durante un estudio de ácido zoledrónico frente a placebo. FACT-G: evaluación funcional del tratamiento del cáncer-general. Weinfurt KP, et al. Ann Oncol 2005;16:579–84.

Los 10 principales problemas de HRQoL
El dolor a largo plazo se considera el principal problema de HRQoL en los pacientes con cáncer con metástasis óseas Los 10 principales problemas de HRQoL 1 Dolor a largo plazo (crónico). 2 Dificultad para desempeñar tareas diarias normales (comprar, tareas domésticas, etc.). 3 Preocupación por tener que depender de otras personas. 4 Preocupación por sufrir una pérdida de movilidad que limite su independencia. 5 Preocupación por la progresión de la enfermedad, el deterioro de su estado y las complicaciones futuras. Patients with cancer and bone metastases report a range of HRQoL issues, spanning physical, emotional and functional parameters as well as treatment expectations.1 This slide shows data from a study in which a list of 61 HRQoL issues was developed from literature searches and interviews with patients and healthcare professionals. These items were developed into a questionnaire that was distributed to patients with bone metastases at five centres in Canada, Australia and Germany.1 A total of 413 patients were interviewed.1 Patients were asked to select 510 items from the list that they felt affected their life most profoundly.1 The number one issue ranked by patients as most profoundly affecting their life was long-term or chronic pain.1 Reference Harris K, Chow E, Zhang L, et al. Patients’ and health care professionals’ evaluation of health-related quality of life issues in bone metastases. Eur J Cancer 2009;45:2510–18. Harris K, et al. Eur J Cancer 2009;45:25108.

El dolor a largo plazo se considera el principal problema de HRQoL en los pacientes con cáncer con metástasis óseas 6 Capacidad de cuidarse. 7 Dificultad para realizar actividades significativas (incluido trabajar). 8 Capacidad para desempeñar funciones (como tareas domésticas y familiares). 9 Carga económica debido a la enfermedad. 10 Esperanza de que el tratamiento reducirá el dolor en la medida de lo posible. Patients with cancer and bone metastases report a range of HRQoL issues, spanning physical, emotional and functional parameters as well as treatment expectations.1 This slide shows data from a study in which a list of 61 HRQoL issues was developed from literature searches and interviews with patients and healthcare professionals. These items were developed into a questionnaire that was distributed to patients with bone metastases at five centres in Canada, Australia and Germany.1 A total of 413 patients were interviewed.1 Patients were asked to select 510 items from the list that they felt affected their life most profoundly.1 The number one issue ranked by patients as most profoundly affecting their life was long-term or chronic pain.1 Reference Harris K, Chow E, Zhang L, et al. Patients’ and health care professionals’ evaluation of health-related quality of life issues in bone metastases. Eur J Cancer 2009;45:2510–18. Harris K, et al. Eur J Cancer 2009;45:25108.

Tratamiento del dolor óseo

Las opciones de tratamiento del dolor óseo incluyen analgésicos opioides y no opioides
Dolor leve Dolor leve-moderado Dolo moderado-intenso AINE Paracetamol Opioides débiles† ± Opioides fuertes‡ ± Fármacos adyuvantes, como corticosteroides, anticonvulsivos y antidepresivos, según proceda. Se debe administrar tratamiento analgésico de acuerdo con la escala analgésica de la OMS según la intensidad del dolor. Treatment options for cancer pain include opioid and non-opioid analgesics in addition to adjuvant drugs, e.g. corticosteroids, anticonvulsants and antidepressants, as appropriate.1 Analgesic treatment should be tailored to the severity of pain, in accordance with the World Health Organization (WHO) analgesic ladder.1 Paracetamol and/or a non-steroidal anti-inflammatory drug (NSAID) is effective for treating mild pain; weak opioids such as codeine, tramadol and dihydrocodeine should be given in combination with non-opioid analgesics for mild-to-moderate pain; and strong opioids, with or without non-opioid analgesics, are recommended for moderate-to-severe pain − oral morphine being the strong opioid of choice. In the presence of renal impairment, all opioids should be used with caution and at reduced doses and frequency.1 Importantly, patients should be informed about cancer pain and encouraged to take an active role in their pain management.1 Reference Ripamonti CI, Santini D, Maranzano E, et al. Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol 2012;23(Suppl 7):vii139−54. AINE: fármaco antiinflamatorio no esteroideo. †Los opioides débiles incluyen codeína, tramadol y dihidrocodeína. ‡La morfina oral es el opioide indicado para el dolor moderado-intenso. Ripamonti CI, et al. Ann Oncol 2012;23(Suppl 7):vii139–54.

En los pacientes con dolor óseo, además de los analgésicos, se recomienda tratamiento dirigido al hueso ± radioterapia Directrices de práctica clínica de la ESMO sobre el tratamiento del dolor oncológico Denosumab, ácido zoledrónico o pamidronato‡ + radioterapia antiálgica TRATAMIENTO ANALGÉSICO SÍ Metástasis óseas sin complicaciones ¿Dolor óseo? NO Denosumab, AC. zoledrónico o pamidronato The European Society for Medical Oncology (ESMO) has developed clinical practice guidelines on the management of cancer pain.1 According to these guidelines, bone-targeted agents (denosumab, zoledronic acid or pamidronate [the latter only in patients with breast cancer]) have an important role in bone pain management in association with analgesic drugs and appropriate use of radiotherapy, radioisotopes and/or surgery.1 Of note, these agents are recommended in the absence of bone pain to delay the occurrence of pain and SREs.1 Reference Ripamonti CI, Santini D, Maranzano E, et al. Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol 2012;23(Suppl 7):vii139−54. Ripamonti CI, et al. Ann Oncol 2012;23(Suppl 7):vii139–54. †Compresión de la médula espinal o fractura inminente; ‡Pamidronato solo en pacientes con cáncer de mama.

En los pacientes con dolor óseo, además de los analgésicos, se recomienda tratamiento dirigido al hueso ± radioterapia Directrices de práctica clínica de la ESMO sobre el tratamiento del dolor oncológico Radioterapia y/o cirugía (cuando sea adecuado) + denosumab, ácido zoledrónico o pamidronato‡ TRATAMIENTO ANALGÉSICO Denosumab, ácido zoledrónico o pamidronato‡ + radioterapia antiálgica TRATAMIENTO ANALGÉSICO SÍ SÍ Metástasis óseas sin complicaciones ¿Dolor óseo? ¿Metástasis óseas complicadas?† NO NO Denosumab, AC. zoledrónico o pamidronato Las mismas estrategias que en las metástasis óseas sin complicaciones ± dolor óseo The European Society for Medical Oncology (ESMO) has developed clinical practice guidelines on the management of cancer pain.1 According to these guidelines, bone-targeted agents (denosumab, zoledronic acid or pamidronate [the latter only in patients with breast cancer]) have an important role in bone pain management in association with analgesic drugs and appropriate use of radiotherapy, radioisotopes and/or surgery.1 Of note, these agents are recommended in the absence of bone pain to delay the occurrence of pain and SREs.1 Reference Ripamonti CI, Santini D, Maranzano E, et al. Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol 2012;23(Suppl 7):vii139−54. Ripamonti CI, et al. Ann Oncol 2012;23(Suppl 7):vii139–54. †Compresión de la médula espinal o fractura inminente; ‡Pamidronato solo en pacientes con cáncer de mama.

En los pacientes con dolor óseo, además de los analgésicos, se recomienda tratamiento dirigido al hueso ± radioterapia Directrices de práctica clínica de la ESMO sobre el tratamiento del dolor oncológico Radioterapia y/o cirugía (cuando sea adecuado) + denosumab, ácido zoledrónico o pamidronato‡ TRATAMIENTO ANALGÉSICO Denosumab, ácido zoledrónico o pamidronato‡ + radioterapia antiálgica TRATAMIENTO ANALGÉSICO Denosumab, ácido zoledrónico o pamidronato SÍ SÍ SÍ Metástasis óseas sin complicaciones ¿Dolor óseo? ¿Metástasis óseas complicadas?† ERE previo: radioterapia, cirugía ósea NO NO NO Denosumab, AC. zoledrónico o pamidronato Las mismas estrategias que en las metástasis óseas sin complicaciones ± dolor óseo Denosumab, ácido zoledrónico o pamidronato The European Society for Medical Oncology (ESMO) has developed clinical practice guidelines on the management of cancer pain.1 According to these guidelines, bone-targeted agents (denosumab, zoledronic acid or pamidronate [the latter only in patients with breast cancer]) have an important role in bone pain management in association with analgesic drugs and appropriate use of radiotherapy, radioisotopes and/or surgery.1 Of note, these agents are recommended in the absence of bone pain to delay the occurrence of pain and SREs.1 Reference Ripamonti CI, Santini D, Maranzano E, et al. Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol 2012;23(Suppl 7):vii139−54. Ripamonti CI, et al. Ann Oncol 2012;23(Suppl 7):vii139–54. †Compresión de la médula espinal o fractura inminente; ‡Pamidronato solo en pacientes con cáncer de mama.

En los pacientes con dolor óseo, además de los analgésicos, se recomienda tratamiento dirigido al hueso ± radioterapia Directrices de práctica clínica de la ESMO sobre el tratamiento del dolor oncológico Radioterapia y/o cirugía (cuando sea adecuado) + denosumab, ácido zoledrónico o pamidronato‡ TRATAMIENTO ANALGÉSICO Denosumab, ácido zoledrónico o pamidronato‡ + radioterapia antiálgica TRATAMIENTO ANALGÉSICO Denosumab, ácido zoledrónico o pamidronato Se recomienda el tratamiento dirigido al hueso, independientemente de la presencia de dolor o ERE previo. Estos fármacos retrasan la aparición y la progresión del dolor, así como el primer ERE y los posteriores. SÍ SÍ SÍ Metástasis óseas sin complicaciones ¿Dolor óseo? ¿Metástasis óseas complicadas?† ERE previo: radioterapia, cirugía ósea NO NO NO Denosumab, AC. zoledrónico o pamidronato Las mismas estrategias que en las metástasis óseas sin complicaciones ± dolor óseo Denosumab, ácido zoledrónico o pamidronato The European Society for Medical Oncology (ESMO) has developed clinical practice guidelines on the management of cancer pain.1 According to these guidelines, bone-targeted agents (denosumab, zoledronic acid or pamidronate [the latter only in patients with breast cancer]) have an important role in bone pain management in association with analgesic drugs and appropriate use of radiotherapy, radioisotopes and/or surgery.1 Of note, these agents are recommended in the absence of bone pain to delay the occurrence of pain and SREs.1 Reference Ripamonti CI, Santini D, Maranzano E, et al. Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol 2012;23(Suppl 7):vii139−54. Ripamonti CI, et al. Ann Oncol 2012;23(Suppl 7):vii139–54. †Compresión de la médula espinal o fractura inminente; ‡Pamidronato solo en pacientes con cáncer de mama.

Se recomienda tratamiento dirigido al hueso en los pacientes con metástasis óseas tanto sintomáticas como asintomáticas Directrices de práctica clínica de la ESMO 2014 sobre la salud ósea en cáncer Pautas sobre el tratamiento dirigido al hueso (▼denosumab o ácido zoledrónico) Inicio Iniciar al diagnosticar la enfermedad ósea metastásica. En todos los pacientes con cáncer de mama o CPRC, tanto si son sintomáticos como si no. En pacientes seleccionados con cáncer de pulmón , cáncer renal y otros tumores sólidos avanzados si la esperanza de vida es > 3 meses y se considera que tienen un riesgo elevado de ERE. ESMO has also developed new clinical practice guidelines in bone health for patients with cancer. These guidelines highlight the value of bone-targeted treatments (denosumab or zoledronic acid) for the prevention of skeletal morbidity in metastatic bone disease.1 Of note, in line with the ESMO cancer pain guidelines,2 the new bone health guidelines recommend considering bone-targeted therapy in patients with bone metastases, whether they are symptomatic or not, in order to delay the first SRE and reduce subsequent complications from metastatic bone disease.1 The initiation of bone-targeted therapy is recommended on diagnosis of metastatic bone disease in all patients with breast cancer or CRPC, irrespective of the presence of symptoms1 Bone-targeted therapy is also recommended in selected patients with advanced lung cancer, renal cancer, and other solid tumours, if they have a life expectancy of more than 3 months and they are considered at high risk of SREs.1 It is recommended that bone-targeted treatment is continued throughout the course of the disease, particularly in patients with progression of underlying bone metastases, recent SREs and/or elevated bone resorption markers.1 References Coleman R, Body JJ, Aapro M, et al. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2014 [Epub ahead of print]. Ripamonti CI, Santini D, Maranzano E, et al. Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol 2012;23(Suppl 7):vii139−54. †Se espera que los resultados de ensayos clínicos que evalúan las posibles aplicaciones clínicas de los marcadores óseos (p. ej., ayudar a identificar pacientes con riesgo elevado de metástasis ósea o progresión de lesión ósea) identifiquen el valor real de los marcadores óseos en la práctica clínica. CPRC: cáncer de próstata resistente a la castración. Coleman R, et al. Ann Oncol 2014 [publicación electrónica antes de impresión]. ▼ Este medicamento está sujeto a una supervisión adicional. Se deben notificar todas las sospechas de reacciones adversas.

Se recomienda tratamiento dirigido al hueso en los pacientes con metástasis óseas tanto sintomáticas como asintomáticas Directrices de práctica clínica de la ESMO 2014 sobre la salud ósea en cáncer Pautas sobre el tratamiento dirigido al hueso (▼denosumab o ácido zoledrónico) Inicio Iniciar al diagnosticar la enfermedad ósea metastásica. En todos los pacientes con cáncer de mama o CPRC, tanto si son sintomáticos como si no. En pacientes seleccionados con cáncer de pulmón , cáncer renal y otros tumores sólidos avanzados si la esperanza de vida es > 3 meses y se considera que tienen un riesgo elevado de ERE. Continuación Continuar indefinidamente durante todo el transcurso de la enfermedad. Se recomienda el tratamiento continuado con progresión de las metástasis óseas, un ERE reciente y/o marcadores de resorción ósea elevados.† ESMO has also developed new clinical practice guidelines in bone health for patients with cancer. These guidelines highlight the value of bone-targeted treatments (denosumab or zoledronic acid) for the prevention of skeletal morbidity in metastatic bone disease.1 Of note, in line with the ESMO cancer pain guidelines,2 the new bone health guidelines recommend considering bone-targeted therapy in patients with bone metastases, whether they are symptomatic or not, in order to delay the first SRE and reduce subsequent complications from metastatic bone disease.1 The initiation of bone-targeted therapy is recommended on diagnosis of metastatic bone disease in all patients with breast cancer or CRPC, irrespective of the presence of symptoms1 Bone-targeted therapy is also recommended in selected patients with advanced lung cancer, renal cancer, and other solid tumours, if they have a life expectancy of more than 3 months and they are considered at high risk of SREs.1 It is recommended that bone-targeted treatment is continued throughout the course of the disease, particularly in patients with progression of underlying bone metastases, recent SREs and/or elevated bone resorption markers.1 References Coleman R, Body JJ, Aapro M, et al. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2014 [Epub ahead of print]. Ripamonti CI, Santini D, Maranzano E, et al. Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol 2012;23(Suppl 7):vii139−54. †Se espera que los resultados de ensayos clínicos que evalúan las posibles aplicaciones clínicas de los marcadores óseos (p. ej., ayudar a identificar pacientes con riesgo elevado de metástasis ósea o progresión de lesión ósea) identifiquen el valor real de los marcadores óseos en la práctica clínica. CPRC: cáncer de próstata resistente a la castración. Coleman R, et al. Ann Oncol 2014 [publicación electrónica antes de impresión]. ▼ Este medicamento está sujeto a una supervisión adicional. Se deben notificar todas las sospechas de reacciones adversas.

Los Bisfosfonatos eficacia analgésica en los pacientes con Dolor Óseo
Resultado (estudios controlados) N.º de estudios N.º de pacientes Tamaño del efecto Odds ratio (IC del 95%)† Proporción de pacientes con alivio del dolor al cabo de 4 semanas 6 408 2,21 (1,19-4,12) Proporción de pacientes con respuesta al dolor al cabo de 8 semanas 1 157 2,57 (0,64-10,31) Proporción de pacientes con alivio del dolor al cabo de 12 semanas 5 634 2,49 (1,38-4,48) Proporción de pacientes con alivio del dolor con la mejor respuesta al cabo de 12 semanas 8 723 2,37 (1,61-3,50) The body of evidence supports some analgesic efficacy of bisphosphonates in patients with bone pain due to bone metastases.1 A Cochrane review of randomised controlled trials of bisphosphonates, with pain and/or analgesic consumption as outcome measures, analysed data for 30 trials with a total of 3682 subjects. Of note, for each outcome examined, there were few studies with available data (see slide for details).1 Among 8 studies with data available for the proportion of patients with pain relief, number needed-to-treat was 11 (95% CI, 6−36) at 4 weeks and 7 (95% CI, 5−12) at 12 weeks.1 Reference Wong R and Wiffen PJ. Bisphosphonates for the relief of pain secondary to bone metastases. Cochrane Database Syst Rev 2002;(2):CD †M-H, aleatorio, IC del 95%. NNT: número necesario a tratar. Los datos proceden de una revisión de Cochrane de 30 estudios controlados aleatorizados con un total de sujetos. Wong R y Wiffen PJ. Cochrane Database Syst Rev 2002;(2):CD

Ensayos pivotales fase III Denosumab frente a Ácido Zoledrónico para la prevención de ERE en pacientes con metástasis óseas de tumores sólidos Análisis del dolor

Tiempo hasta el empeoramiento del dolor.†
Variables de dolor seleccionadas en ensayos de prevención de ERE con denosumab Intensidad del dolor Tiempo hasta el empeoramiento del dolor.† Tiempo hasta dolor moderado o intenso entre los pacientes sin dolor o con dolor leve a nivel basal. There are multiple ways to assess pain in clinical trials; the denosumab Phase III SRE prevention trials quantified the patient-reported outcomes of pain severity, pain interference and analgesic use, in addition to HRQoL.1 Pain severity endpoints included time to moderate or severe pain (BPI−SF worst pain score > 4 points) among patients with no or mild pain (BPI−SF worst pain score 0–4 points) at baseline.1 Reference von Moos R, Body JJ, Egerdie B, et al. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer 2013;21:3497507. von Moos R, et al. Support Care Cancer 2013;21:3497507. †Según el BPI-SF de 11 puntos. ‡Según el algoritmo de cuantificación de analgésicos (AQA) de 8 categorías. * 7 dominios de interferencia del dolor en el BPI-SF.

(general, andar, trabajo),
Variables de dolor seleccionadas en ensayos de prevención de ERE con denosumab Intensidad del dolor Tiempo hasta el empeoramiento del dolor.† Tiempo hasta dolor moderado o intenso entre los pacientes sin dolor o con dolor leve a nivel basal. Interferencia del dolor Cambio clínicamente significativo en la interferencia del dolor: actividad (general, andar, trabajo), afectación (estado de ánimo, relaciones, alegría de vivir) y global (actividad + afectación + sueño).* There are multiple ways to assess pain in clinical trials; the denosumab Phase III SRE prevention trials quantified the patient-reported outcomes of pain severity, pain interference and analgesic use, in addition to HRQoL.1 Pain severity endpoints included time to moderate or severe pain (BPI−SF worst pain score > 4 points) among patients with no or mild pain (BPI−SF worst pain score 0–4 points) at baseline.1 Reference von Moos R, Body JJ, Egerdie B, et al. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer 2013;21:3497507. von Moos R, et al. Support Care Cancer 2013;21:3497507. †Según el BPI-SF de 11 puntos. ‡Según el algoritmo de cuantificación de analgésicos (AQA) de 8 categorías. * 7 dominios de interferencia del dolor en el BPI-SF.

Variables de dolor seleccionadas en ensayos de prevención de ERE con denosumab
Intensidad del dolor Tiempo hasta el empeoramiento del dolor.† Tiempo hasta dolor moderado o intenso entre los pacientes sin dolor o con dolor leve a nivel basal. Interferencia del dolor Cambio clínicamente significativo en la interferencia del dolor: actividad (general, andar, trabajo), afectación (estado de ánimo, relaciones, alegría de vivir) y global (actividad + afectación + sueño).* Uso de analgésicos Progresión de los pacientes desde la ausencia o el escaso uso de analgésicos (AQA  2) hasta el uso de opioides fuertes (AQA ≥ 3).‡ There are multiple ways to assess pain in clinical trials; the denosumab Phase III SRE prevention trials quantified the patient-reported outcomes of pain severity, pain interference and analgesic use, in addition to HRQoL.1 Pain severity endpoints included time to moderate or severe pain (BPI−SF worst pain score > 4 points) among patients with no or mild pain (BPI−SF worst pain score 0–4 points) at baseline.1 Reference von Moos R, Body JJ, Egerdie B, et al. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer 2013;21:3497507. von Moos R, et al. Support Care Cancer 2013;21:3497507. †Según el BPI-SF de 11 puntos. ‡Según el algoritmo de cuantificación de analgésicos (AQA) de 8 categorías. * 7 dominios de interferencia del dolor en el BPI-SF.

Denosumab retrasó el empeoramiento del dolor en 1,8 meses en comparación con el ácido zoledrónico
Tiempo hasta el dolor moderado o intenso (> 4 puntos) entre los pacientes sin dolor o con dolor leve (0-4 puntos) a nivel basal (n = 2.683)† HR = 0,83 (IC del 95%, 0,760,92) p < 0,001 + 1,8 meses Mediana de tiempo desde la ausencia de dolor o dolor leve hasta un dolor moderado o intenso (meses) 2683 (52%) of 5198 patients included in the pooled pain analysis reported no or mild pain (BPI−SF worst pain score 0–4 points) at baseline. Among these patients, denosumab delayed the median time to onset of moderate or severe pain (> 4 points) by 1.8 months compared with zoledronic acid (6.5 vs 4.7 months) and reduced the risk of experiencing moderate or severe pain by 17% (HR, 0.83; P <0.001).1 Reference von Moos R, Body JJ, Egerdie B, et al. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer 2013;21:3497507. Ácido zoledrónico Denosumab von Moos R, et al. Support Care Cancer 2013;21:3497507. †Peor puntuación del dolor del BPISF.

Empeoramiento del dolor en los pacientes tratados con denosumab frente al ácido zoledrónico por tipo de tumor HR = 0,78 (IC del 95%, 0,670,92) p = 0,0024 + 119 días Denosumab Ácido zoledrónico HR = 0,81 (IC del 95%, 0,670,99) p = 0,04 + 40 días Mediana de tiempo desde la ausencia de dolor o dolor leve hasta un dolor moderado o intenso (meses)† This slide shows time to pain worsening data from the individual Phase III SRE prevention studies in breast cancer, prostate cancer and other solid tumours (excluding breast and prostate; not including multiple myeloma patients). In the breast cancer study, in patients with no or mild pain at baseline (n = 1042), denosumab delayed the development of moderate or severe pain by 119 days compared with zoledronic acid (denosumab, median 295 days; zoledronic acid, median 176 days; HR, 0.78; 95% CI, 0.670.92, P = ), representing a 22% risk reduction.1 In the prostate cancer study, among patients with no or mild pain at baseline, denosumab delayed the development of moderate or severe pain by 29 days compared with zoledronic acid (denosumab, median 177 days; zoledronic acid, median 148 days; hazard ratio, 0.89; 95% CI, 0.771.04; P = 0.142); the difference did not reach statistical significance in this study.2 In patients with other solid tumours, among those with no or mild pain at baseline, denosumab delayed the development of moderate or severe pain by 40 days compared with zoledronic acid (denosumab, median 143 days; zoledronic acid, median 103 days; HR, 0.81; 95% CI, 0.670.99; P = 0.04), representing a 19% risk reduction.3 Note, for comparison, data from the other solid tumours study have been converted from months to days based on 1 month = 30.4 days. References Cleeland CS, Body JJ, Stopeck A, et al. Pain outcomes in patients with advanced breast cancer and bone metastases: results from a randomized, double-blind study of denosumab and zoledronic acid. Cancer 2013;119:8328. Brown JE, Cleeland CS, Fallowfield LJ, et al. Pain outcomes in patients with bone metastases from castrate-resistant prostate cancer: results from a phase 3 trial of denosumab vs. zoledronic acid. European Association Urology Annual Congress. Vienna, Austria. March 18–22, Abstract 1091 (and poster). Vadhan-Raj S, von Moos R, Fallowfield LJ, et al. Clinical benefit in patients with metastatic bone disease: results of a phase 3 study of denosumab versus zoledronic acid. Ann Oncol 2012;23:304551. Mama 1 Próstata 2 Otros tumores sólidos ‡ 3 1. Cleeland CS, et al. Cancer 2013;119:8328; 2. Brown JE, et al. EAU 2011: resumen 1091 (y póster); 3. Vadhan-Raj S, et al. Ann Oncol 2012;23:304551. †Tiempo hasta la peor puntuación del dolor > 4 puntos entre los pacientes sin dolor o con dolor leve (0-4 puntos) a nivel basal. ‡Excepto el cáncer de mama y próstata. Datos convertidos a partir de meses considerando que 1 mes tiene 30,4 días.

Puntuación de la actividad Puntuación de la afectación
Mediana de tiempo hasta un aumento de la interferencia del dolor significativamente mayor con denosumab que con ácido zoledrónico para todas las 3 medidas de interferencia Tiempo hasta un aumento clínicamente significativo (es decir, aumento ≥ 2 puntos) en la interferencia del dolor entre los pacientes sin dolor o con dolor leve a nivel basal. Puntuación de la actividad Puntuación de la afectación Puntuación global 100 60 80 BL Mes del estudio 3 6 9 20 40 Mediana (meses) (n = 2.524) HR = 0,85 (IC del 95%, 0,77-0,94) p = 0,002 Denosumab 7,6 Ácido zoledrónico 6,0 BL Mes del estudio 3 6 9 Mediana (meses) (n = 2.547) Denosumab 9,2 Ácido zoledrónico 7,4 BL Mes del estudio 3 6 9 Mediana (meses) (n = 2.613) HR = 0,83 (IC del 95%, 0,75-0,92) p < 0,001 Denosumab 10,3 Ácido zoledrónico 7,7 Pacientes sin un aumento ≥ 2 puntos respecto al valor basal (%) HR = 0,86 (IC del 95%, 0,77-0,95) p = 0,003 Among patients with no or mild pain at baseline, median time to increased pain interference was significantly longer with denosumab compared with zoledronic acid for all three pain interference measures (activity, affect and overall).1 Denosumab delayed the median time to a clinically meaningful increase in pain interference from baseline by:1 1.6 months (HR, 0.85; P = 0.002) for activity 1.8 months (HR, 0.86; P = 0.003) for affect 2.6 months (HR 0.83; P < 0.001) for overall pain interference. Reference von Moos R, Body JJ, Egerdie B, et al. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer 2013;21:3497507. Actividad general Capacidad para andar Trabajo normal Estado de ánimo Relaciones interpersonales Alegría de vivir Actividad + afectación + sueño von Moos R, et al. Support Care Cancer 2013;21:3497507. BL: basal; KM: Kaplan–Meier.

Menos pacientes han experimentado un aumento de la interferencia del dolor con denosumab que con ácido zoledrónico Pacientes con un aumento clínicamente significativo (es decir, aumento ≥ 2 puntos) en la interferencia del dolor global con respecto al valor basal Denosumab (n = 2.469) Ácido zoledrónico (n = 2.443) Diferencia relativa media, -10,4% p = 0,040 global† Pacientes en riesgo (%) Among all patients at risk, fewer patients on denosumab than zoledronic acid experienced clinically meaningful increase (ie ≥ 2-point increase) from baseline in overall pain interference score, with an average relative difference favouring denosumab of -10.4% (overall treatment difference P = by Generalised Estimating Equation).1 Reference von Moos R, Body JJ, Egerdie B, et al. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer 2013;21:3497507. Mes del estudio von Moos R, et al. Support Care Cancer 2013;21:3497507. * El análisis excluye a los pacientes con mieloma múltiple. †Denosumab frente a ácido zoledrónico mediante la ecuación de estimación generalizada.

Menos pacientes han progresado desde la ausencia de uso o el escaso uso de analgésicos hasta el uso de opioides fuertes con denosumab que con ácido zoledrónico Progresión de los pacientes desde la ausencia de uso o el escaso uso de analgésicos (AQA ≤ 2) hasta el uso de opioides fuertes (AQA ≥ 3)*† Denosumab (n = 2.174) Ácido zoledrónico (n = 2.144) Diferencia relativa media, -13,4% p = 0,041 global‡ Proporción de pacientes (%) Fewer patients on denosumab progressed from no or low analgesic use (AQA ≤ 2 points) to strong opioid use (AQA ≥ 3 points) compared with zoledronic acid, with an average relative difference of -13.4% (overall treatment P = by Generalised Estimating Equation).1 Reference von Moos R, Body JJ, Egerdie B, et al. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer 2013;21:3497507. Mes del estudio von Moos R, et al. Support Care Cancer 2013;21:3497507. * El análisis excluye a los pacientes con mieloma múltiple. †OME ≥ 75 mg/día. ‡Denosumab frente a ácido zoledrónico mediante la ecuación de estimación generalizada.

Menos pacientes han experimentado un empeoramiento de la HRQoL con denosumab que con ácido zoledrónico Proporción de pacientes en riesgo con una reducción en la puntuación total de la FACT-G ≥ 5 puntos respecto al valor basal Denosumab (n = 2.603) Ácido zoledrónico (n = 2.579) Diferencia relativa media, -4,1% p = 0,005 global† Proporción de pacientes (%) Among all patients at risk, fewer patients on denosumab than zoledronic acid experienced clinically meaningful worsening (≥ 5-point reduction) in HRQoL, with an average relative difference of -4.1% favouring denosumab (overall treatment difference P = by Generalised Estimating Equation).1 Reference von Moos R, Body JJ, Egerdie B, et al. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer 2013;21:3497507. Mes del estudio von Moos R, et al. Support Care Cancer 2013;21:3497507. †Denosumab frente a ácido zoledrónico mediante la ecuación de estimación generalizada.

Denosumab mejora la calidad de vida relacionada con la salud (HRQoL)
120 mg de denosumab Q4W (n = 956) 4 mg de ácido zoledrónico (n = 952) 40 * * * p < 0,05 * 30 10% Proporción de pacientes con mejora de la HRQoL (%) 20 Mejora de la HRQoL en la población global: aumento relativo promedio con denosumab frente a ácido zoledrónico 10 The graph shows the proportion of patients with clinically meaningful improvement of HRQoL (≥ 5-point increase in FACT-G total score from baseline)1 Denosumab also significantly improved HRQoL versus zoledronic acid in patients with no or mild pain at baseline1 Reference Martin M et al. Clin Cancer Res 2012;18:4841–9 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Mes del estudio Una mayor proporción de pacientes con cáncer de mama y metástasis óseas experimentaron una mejor HRQoL cuando se trataron con denosumab que cuando se trataron con ácido zoledrónico. Q4W: cada 4 semanas. Martin et al. Clin Cancer Res 2012;18:4841–9

Conclusiones Necesidad no cubierta Las metástasis óseas son la causa más frecuente de dolor en los pacientes con cáncer . Los ERE asociados pueden tener un impacto significativo en la calidad de vida de los pacientes.1,2 Bone metastases are the most common cause of pain in advanced cancer patients and associated SREs can significantly impact patients’ quality of life.1,2 Denosumab was compared with zoledronic acid for SRE prevention in 3 large randomised clinical trials of patients with bone metastases from solid tumours or multiple myeloma. In an integrated analysis of data from these trials, denosumab significantly reduced the total number of SREs vs zoledronic acid and delayed the time to first on-study SRE to almost 28 months.3 A pooled analysis of data for pain endpoints in patients with solid tumours showed that time to moderate-to-severe pain (among patients with no or mild pain at baseline) was 6.5 months in patients on denosumab − a delay of 1.8 months vs zoledronic acid.4 Additionally, fewer patients on denosumab than zoledronic acid had a clinically meaningful increase in pain interference and fewer patients on denosumab progressed from no or low analgesic use to strong opioid use.4 In line with these findings, fewer patients on denosumab than zoledronic acid experienced worsening of HRQoL.4 The available data has led to the recommendation, in ESMO clinical practice guidelines, that bone-targeted therapy with denosumab or zoledronic acid should be started in patients with bone metastases, whether they are symptomatic or not ie regardless of the presence of pain or prior SRE.5,6 References Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997;69:1−18. Weinfurt KP, Li Y, Castel LD, et al. The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol 2005;16:579–84. Lipton A, Siena S, Rader M, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer 2012;48:3082−92. von Moos R, Body JJ, Egerdie B, et al. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer 2013;21:3497507. Ripamonti CI, Santini D, Maranzano E, et al. Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol 2012;23(Suppl 7):vii139−54. Coleman R, Body JJ, Aapro M, et al. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2014 [Epub ahead of print]. 1. Mercadante S. Pain 1997;69:1−18; 2. Weinfurt KP, et al. Ann Oncol 2005;16:579–84; 3. Lipton A, et al. Eur J Cancer 2012;48:3082–92; 4. von Moos R, et al. Support Care Cancer 2013;21:3497507; 5. Ripamonti CI, et al. Ann Oncol 2012;23(Suppl 7):vii139–54; 6. Coleman R, et al. Ann Oncol 2014 [publicación electrónica antes de impresión]. †Entre los pacientes sin dolor o con dolor leve a nivel basal.

Conclusiones Necesidad no cubierta Las metástasis óseas son la causa más frecuente de dolor en los pacientes con cáncer avanzado y los ERE asociados pueden tener un impacto significativo en la calidad de vida de los pacientes.1,2 Prevención de ERE Denosumab ha demostrado ser superior al ácido zoledrónico para prevenir los ERE, ya que reduce significativamente el número total de ERE y retrasa el tiempo hasta el primer ERE en casi 28 meses.3 Bone metastases are the most common cause of pain in advanced cancer patients and associated SREs can significantly impact patients’ quality of life.1,2 Denosumab was compared with zoledronic acid for SRE prevention in 3 large randomised clinical trials of patients with bone metastases from solid tumours or multiple myeloma. In an integrated analysis of data from these trials, denosumab significantly reduced the total number of SREs vs zoledronic acid and delayed the time to first on-study SRE to almost 28 months.3 A pooled analysis of data for pain endpoints in patients with solid tumours showed that time to moderate-to-severe pain (among patients with no or mild pain at baseline) was 6.5 months in patients on denosumab − a delay of 1.8 months vs zoledronic acid.4 Additionally, fewer patients on denosumab than zoledronic acid had a clinically meaningful increase in pain interference and fewer patients on denosumab progressed from no or low analgesic use to strong opioid use.4 In line with these findings, fewer patients on denosumab than zoledronic acid experienced worsening of HRQoL.4 The available data has led to the recommendation, in ESMO clinical practice guidelines, that bone-targeted therapy with denosumab or zoledronic acid should be started in patients with bone metastases, whether they are symptomatic or not ie regardless of the presence of pain or prior SRE.5,6 References Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997;69:1−18. Weinfurt KP, Li Y, Castel LD, et al. The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol 2005;16:579–84. Lipton A, Siena S, Rader M, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer 2012;48:3082−92. von Moos R, Body JJ, Egerdie B, et al. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer 2013;21:3497507. Ripamonti CI, Santini D, Maranzano E, et al. Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol 2012;23(Suppl 7):vii139−54. Coleman R, Body JJ, Aapro M, et al. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2014 [Epub ahead of print]. 1. Mercadante S. Pain 1997;69:1−18; 2. Weinfurt KP, et al. Ann Oncol 2005;16:579–84; 3. Lipton A, et al. Eur J Cancer 2012;48:3082–92; 4. von Moos R, et al. Support Care Cancer 2013;21:3497507; 5. Ripamonti CI, et al. Ann Oncol 2012;23(Suppl 7):vii139–54; 6. Coleman R, et al. Ann Oncol 2014 [publicación electrónica antes de impresión]. †Entre los pacientes sin dolor o con dolor leve a nivel basal.

Conclusiones Necesidad no cubierta Las metástasis óseas son la causa más frecuente de dolor en los pacientes con cáncer avanzado y los ERE asociados pueden tener un impacto significativo en la calidad de vida de los pacientes.1,2 Prevención de ERE Denosumab ha demostrado ser superior al ácido zoledrónico para prevenir los ERE, ya que reduce significativamente el número total de ERE y retrasa el tiempo hasta el primer ERE durante el estudio en casi 28 meses.3 Empeoramiento del dolor El tiempo hasta el dolor moderado o intenso fue de 6,5 meses en los pacientes tratados con denosumab†, un retraso de 1,8 meses en comparación con el ácido zoledrónico.3 Además, menos pacientes tratados con denosumab han experimentado un aumento de la interferencia del dolor. Bone metastases are the most common cause of pain in advanced cancer patients and associated SREs can significantly impact patients’ quality of life.1,2 Denosumab was compared with zoledronic acid for SRE prevention in 3 large randomised clinical trials of patients with bone metastases from solid tumours or multiple myeloma. In an integrated analysis of data from these trials, denosumab significantly reduced the total number of SREs vs zoledronic acid and delayed the time to first on-study SRE to almost 28 months.3 A pooled analysis of data for pain endpoints in patients with solid tumours showed that time to moderate-to-severe pain (among patients with no or mild pain at baseline) was 6.5 months in patients on denosumab − a delay of 1.8 months vs zoledronic acid.4 Additionally, fewer patients on denosumab than zoledronic acid had a clinically meaningful increase in pain interference and fewer patients on denosumab progressed from no or low analgesic use to strong opioid use.4 In line with these findings, fewer patients on denosumab than zoledronic acid experienced worsening of HRQoL.4 The available data has led to the recommendation, in ESMO clinical practice guidelines, that bone-targeted therapy with denosumab or zoledronic acid should be started in patients with bone metastases, whether they are symptomatic or not ie regardless of the presence of pain or prior SRE.5,6 References Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997;69:1−18. Weinfurt KP, Li Y, Castel LD, et al. The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol 2005;16:579–84. Lipton A, Siena S, Rader M, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer 2012;48:3082−92. von Moos R, Body JJ, Egerdie B, et al. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer 2013;21:3497507. Ripamonti CI, Santini D, Maranzano E, et al. Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol 2012;23(Suppl 7):vii139−54. Coleman R, Body JJ, Aapro M, et al. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2014 [Epub ahead of print]. 1. Mercadante S. Pain 1997;69:1−18; 2. Weinfurt KP, et al. Ann Oncol 2005;16:579–84; 3. Lipton A, et al. Eur J Cancer 2012;48:3082–92; 4. von Moos R, et al. Support Care Cancer 2013;21:3497507; 5. Ripamonti CI, et al. Ann Oncol 2012;23(Suppl 7):vii139–54; 6. Coleman R, et al. Ann Oncol 2014 [publicación electrónica antes de impresión]. †Entre los pacientes sin dolor o con dolor leve a nivel basal.

Conclusiones Uso de analgésicos
Necesidad no cubierta Las metástasis óseas son la causa más frecuente de dolor en los pacientes con cáncer avanzado y los ERE asociados pueden tener un impacto significativo en la calidad de vida de los pacientes.1,2 Prevención de ERE Denosumab ha demostrado ser superior al ácido zoledrónico para prevenir los ERE, ya que reduce significativamente el número total de ERE y retrasa el tiempo hasta el primer ERE durante el estudio en casi 28 meses.3 Empeoramiento del dolor El tiempo hasta el dolor moderado o intenso fue de 6,5 meses en los pacientes tratados con denosumab†, un retraso de 1,8 meses en comparación con el ácido zoledrónico.3 Además, menos pacientes tratados con denosumab han experimentado un aumento de la interferencia del dolor. Uso de analgésicos Menos pacientes han progresado desde la ausencia del uso de analgésicos hasta el uso de opioides fuertes con denosumab que con ácido zoledrónico.4 Bone metastases are the most common cause of pain in advanced cancer patients and associated SREs can significantly impact patients’ quality of life.1,2 Denosumab was compared with zoledronic acid for SRE prevention in 3 large randomised clinical trials of patients with bone metastases from solid tumours or multiple myeloma. In an integrated analysis of data from these trials, denosumab significantly reduced the total number of SREs vs zoledronic acid and delayed the time to first on-study SRE to almost 28 months.3 A pooled analysis of data for pain endpoints in patients with solid tumours showed that time to moderate-to-severe pain (among patients with no or mild pain at baseline) was 6.5 months in patients on denosumab − a delay of 1.8 months vs zoledronic acid.4 Additionally, fewer patients on denosumab than zoledronic acid had a clinically meaningful increase in pain interference and fewer patients on denosumab progressed from no or low analgesic use to strong opioid use.4 In line with these findings, fewer patients on denosumab than zoledronic acid experienced worsening of HRQoL.4 The available data has led to the recommendation, in ESMO clinical practice guidelines, that bone-targeted therapy with denosumab or zoledronic acid should be started in patients with bone metastases, whether they are symptomatic or not ie regardless of the presence of pain or prior SRE.5,6 References Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997;69:1−18. Weinfurt KP, Li Y, Castel LD, et al. The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol 2005;16:579–84. Lipton A, Siena S, Rader M, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer 2012;48:3082−92. von Moos R, Body JJ, Egerdie B, et al. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer 2013;21:3497507. Ripamonti CI, Santini D, Maranzano E, et al. Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol 2012;23(Suppl 7):vii139−54. Coleman R, Body JJ, Aapro M, et al. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2014 [Epub ahead of print]. 1. Mercadante S. Pain 1997;69:1−18; 2. Weinfurt KP, et al. Ann Oncol 2005;16:579–84; 3. Lipton A, et al. Eur J Cancer 2012;48:3082–92; 4. von Moos R, et al. Support Care Cancer 2013;21:3497507; 5. Ripamonti CI, et al. Ann Oncol 2012;23(Suppl 7):vii139–54; 6. Coleman R, et al. Ann Oncol 2014 [publicación electrónica antes de impresión]. †Entre los pacientes sin dolor o con dolor leve a nivel basal.

Conclusiones Necesidad no cubierta Las metástasis óseas son la causa más frecuente de dolor en los pacientes con cáncer avanzado y los ERE asociados pueden tener un impacto significativo en la calidad de vida de los pacientes.1,2 Prevención de ERE Denosumab ha demostrado ser superior al ácido zoledrónico para prevenir los ERE, ya que reduce significativamente el número total de ERE y retrasa el tiempo hasta el primer ERE durante el estudio en casi 28 meses.3 Empeoramiento del dolor El tiempo hasta el dolor moderado o intenso fue de 6,5 meses en los pacientes tratados con denosumab†, un retraso de 1,8 meses en comparación con el ácido zoledrónico.3 Además, menos pacientes tratados con denosumab han experimentado un aumento de la interferencia del dolor. Uso de analgésicos Menos pacientes han progresado desde la ausencia de uso o el escaso uso de analgésicos hasta el uso de opioides fuertes con denosumab que con ácido zoledrónico.4 HRQoL Menos pacientes han experimentado un empeoramiento de la HRQoL con denosumab que con ácido zoledrónico.4 Bone metastases are the most common cause of pain in advanced cancer patients and associated SREs can significantly impact patients’ quality of life.1,2 Denosumab was compared with zoledronic acid for SRE prevention in 3 large randomised clinical trials of patients with bone metastases from solid tumours or multiple myeloma. In an integrated analysis of data from these trials, denosumab significantly reduced the total number of SREs vs zoledronic acid and delayed the time to first on-study SRE to almost 28 months.3 A pooled analysis of data for pain endpoints in patients with solid tumours showed that time to moderate-to-severe pain (among patients with no or mild pain at baseline) was 6.5 months in patients on denosumab − a delay of 1.8 months vs zoledronic acid.4 Additionally, fewer patients on denosumab than zoledronic acid had a clinically meaningful increase in pain interference and fewer patients on denosumab progressed from no or low analgesic use to strong opioid use.4 In line with these findings, fewer patients on denosumab than zoledronic acid experienced worsening of HRQoL.4 The available data has led to the recommendation, in ESMO clinical practice guidelines, that bone-targeted therapy with denosumab or zoledronic acid should be started in patients with bone metastases, whether they are symptomatic or not ie regardless of the presence of pain or prior SRE.5,6 References Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997;69:1−18. Weinfurt KP, Li Y, Castel LD, et al. The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol 2005;16:579–84. Lipton A, Siena S, Rader M, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer 2012;48:3082−92. von Moos R, Body JJ, Egerdie B, et al. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer 2013;21:3497507. Ripamonti CI, Santini D, Maranzano E, et al. Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol 2012;23(Suppl 7):vii139−54. Coleman R, Body JJ, Aapro M, et al. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2014 [Epub ahead of print]. 1. Mercadante S. Pain 1997;69:1−18; 2. Weinfurt KP, et al. Ann Oncol 2005;16:579–84; 3. Lipton A, et al. Eur J Cancer 2012;48:3082–92; 4. von Moos R, et al. Support Care Cancer 2013;21:3497507; 5. Ripamonti CI, et al. Ann Oncol 2012;23(Suppl 7):vii139–54; 6. Coleman R, et al. Ann Oncol 2014 [publicación electrónica antes de impresión]. †Entre los pacientes sin dolor o con dolor leve a nivel basal.

Conclusiones Necesidad no cubierta Las metástasis óseas son la causa más frecuente de dolor en los pacientes con cáncer avanzado y los ERE asociados pueden tener un impacto significativo en la calidad de vida de los pacientes.1,2 Prevención de ERE Denosumab ha demostrado ser superior al ácido zoledrónico para prevenir los ERE, ya que reduce significativamente el número total de ERE y retrasa el tiempo hasta el primer ERE durante el estudio en casi 28 meses.3 Empeoramiento del dolor El tiempo hasta el dolor moderado o intenso fue de 6,5 meses en los pacientes tratados con denosumab†, un retraso de 1,8 meses en comparación con el ácido zoledrónico.3 Además, menos pacientes tratados con denosumab han experimentado un aumento de la interferencia del dolor. Uso de analgésicos Menos pacientes han progresado desde la ausencia de uso o el escaso uso de analgésicos hasta el uso de opioides fuertes con denosumab que con ácido zoledrónico.4 HRQoL Menos pacientes han experimentado un empeoramiento de la HRQoL con denosumab que con ácido zoledrónico.4 Pautas Se debe iniciar el tratamiento dirigido al hueso (denosumab o ácido zoledrónico) en pacientes con metástasis óseas tanto sin son sintomáticas como si no.5,6 Bone metastases are the most common cause of pain in advanced cancer patients and associated SREs can significantly impact patients’ quality of life.1,2 Denosumab was compared with zoledronic acid for SRE prevention in 3 large randomised clinical trials of patients with bone metastases from solid tumours or multiple myeloma. In an integrated analysis of data from these trials, denosumab significantly reduced the total number of SREs vs zoledronic acid and delayed the time to first on-study SRE to almost 28 months.3 A pooled analysis of data for pain endpoints in patients with solid tumours showed that time to moderate-to-severe pain (among patients with no or mild pain at baseline) was 6.5 months in patients on denosumab − a delay of 1.8 months vs zoledronic acid.4 Additionally, fewer patients on denosumab than zoledronic acid had a clinically meaningful increase in pain interference and fewer patients on denosumab progressed from no or low analgesic use to strong opioid use.4 In line with these findings, fewer patients on denosumab than zoledronic acid experienced worsening of HRQoL.4 The available data has led to the recommendation, in ESMO clinical practice guidelines, that bone-targeted therapy with denosumab or zoledronic acid should be started in patients with bone metastases, whether they are symptomatic or not ie regardless of the presence of pain or prior SRE.5,6 References Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997;69:1−18. Weinfurt KP, Li Y, Castel LD, et al. The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol 2005;16:579–84. Lipton A, Siena S, Rader M, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer 2012;48:3082−92. von Moos R, Body JJ, Egerdie B, et al. Pain and health-related quality of life in patients with advanced solid tumours and bone metastases: integrated results from three randomized, double-blind studies of denosumab and zoledronic acid. Support Care Cancer 2013;21:3497507. Ripamonti CI, Santini D, Maranzano E, et al. Management of cancer pain: ESMO Clinical Practice Guidelines. Ann Oncol 2012;23(Suppl 7):vii139−54. Coleman R, Body JJ, Aapro M, et al. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2014 [Epub ahead of print]. 1. Mercadante S. Pain 1997;69:1−18; 2. Weinfurt KP, et al. Ann Oncol 2005;16:579–84; 3. Lipton A, et al. Eur J Cancer 2012;48:3082–92; 4. von Moos R, et al. Support Care Cancer 2013;21:3497507; 5. Ripamonti CI, et al. Ann Oncol 2012;23(Suppl 7):vii139–54; 6. Coleman R, et al. Ann Oncol 2014 [publicación electrónica antes de impresión]. †Entre los pacientes sin dolor o con dolor leve a nivel basal.

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Ana Lluch Hospital Clínico Universitario Valencia

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