PEDRO SÁNCHEZ ROVIRA COMPLEJO HOSPITALARIO DE JAÉN
Maintenance therapy is the treatment of cancer with medication, typically following an initial round of treatment. Maintenance treatment may include chemotherapy, hormonal therapy or targeted therapy. Maintenance therapy is used for the following reasons: To prevent or delay the cancer s return if the cancer is in complete remission after initial treatment. Complete remission means doctors cannot find cancer and you have no symptoms. To slow the growth of advanced cancer after initial treatment. This can help shrink the cancer, which is called a partial remission. In this situation, maintenance therapy is not used to cure the cancer, but it can lengthen a person s life.
HORMONOTERAPIA
QUIMIOTERAPIA
Relación entre la duración del tratamiento y la supervivencia Duración de la quimioterapia para el Cáncer de Mama Metastásico: Revisión sistemática y meta-análisis de ensayos clínicos randomizados SLP SG Genari et al, J Clin Oncol 2011; 29:2144-9
MAVERICK: fase fase II aleatorizado II aleatorizado de Vinorelbina de Vinorelbina Oral Metronómica Oral como Metronómica tratamiento como de mantenimiento tratamiento tras de 1ª mantenimiento línea con Taxanos tras en 1ª línea con Taxanos CMM HER2 en negativo CMM HER2 negativo CMM HER2 tratado en 1ª L. con taxanos. Mínimo 4 ciclos Si CE 2:1 N = 81 N = 40 VRL oral 50 mg D1, 3 & 5/sem Ciclos de 3 semanas Mejor tratamiento de soporte* Hasta progresión Hasta toxicidad inaceptable Hasta decisión del paciente Hasta decisión del investigador *En el brazo control se permite una terapia endocrina para pacientes RRHH positivos; no se permite QT ni Terapias dirigidas Objetivo primario: Supervivencia Libre de Progresión (SLP) PROMOTORES: FISABIO + ATRIO
TERAPIAS DIRIGIDAS
BEATRICE: Phase III Trial of Adjuvant Bevacizumab in Triple-Negative Breast Cancer BEATRICE study design Eligibility criteria: Resected triple-negative (centrally confirmed) invasive early breast cancer Primary endpoint: DFS Secondary endpoints: OS, breast cancer-free interval, DFS, distant DFS, safety, biomarkers (N=2591) R A N D O M I Z E 4-8 cycles of standard chemotherapy (investigator s choice) 4-8 cycles of standard chemotherapy (investigator s choice) + bevacizumab 5 mg/kg/wk equivalent for 1 year duration Chemotherapy options: Taxane-based ( 4 cycles) Anthracycline-based ( 4 cycles) Anthracycline + taxane (3-4 cycles each) Cameron et al., SABCS 2012; abstract S6-5
BEATRICE: Phase III Trial of Adjuvant Bevacizumab in Triple-Negative Breast Cancer Efficacy results Outcome None of the subgroups examined (age, baseline ECOG performance status, region, race, menopausal status, tumor size, # of positive LNs, adjuvant chemotherapy, HR status, and surgery) showed a significant effect on invasive DFS Safety results Chemo alone (n=1290) Chemo + bevacizumab (n=1301) HR (95%CI) P-value 3-yr invasive DFS 82.7% 83.7% 0.87 (0.72-1.07).18 OS -- -- 0.84 (0.64-1.12).23 Adverse events Any AE Grade 3 AE Grade 5 AE AE leading to chemo and/or bev discontinuation AE leading to bev discontinuation Chemo alone (n=1271) 99% 57% 0.2% 2% -- Chemo + bevacizumab (n=1288) 99% 72% 0.3% 20% 18% Cameron et al., SABCS 2012; abstract S6-5
BEATRICE Trial: Biomarker Results Biomarker analysis performed to investigate potential predictive markers of benefit from adjuvant bevacizumab Sub-study included 45% of total patient population Evaluated correlation of biomarkers with invasive disease-free survival Baseline Plasma Concentration HR* P-Value Median VEGF-A High 0.81 Low 0.89 3 rd Quartile VEGF-A High 0.64 Low 0.92 Median VEGFR-2 High.61 Low 1.24 * HR <1.0 indicates CT plus Bev better than CT alone.7415.3551.0291 Carmeliet et al., SABCS 2012; abstract P3-06-34
PERSPECTIVAS DE FUTURO
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CONCLUSIONES La terapia de mantenimineto constituye una práctica habitual en el tratamiento del cáncer de mama. La no existencia de estudios randomizados no permite afirmar que no sea una práctica ineficaz. La existencia de dianas específicas con fármacos dirigidos aumenta las expectativas de conseguir aumentos significativos en los tiempos a la progresión. Debemos ser conscientes de la heterogeneidad y plasticidad tumoral que con ayuda de técnicas de biopsia liquida no permitan diseños de ensayos adaptativos que impacten de forma significativa en la supervivencia.