Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer.

BACKGROUND: AKT pathway activation is implicated in endocrine-therapy resistance. Data on the efficacy and safety of the AKT inhibitor capivasertib, as an addition to fulvestrant therapy, in patients with hormone receptor-positive advanced breast cancer are limited. METHODS: In a phase 3, randomized, double-blind trial, we enrolled eligible pre-, peri-, and postmenopausal women and men with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer who had had a relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy. Patients were randomly assigned in a 1:1 ratio to receive capivasertib plus fulvestrant or placebo plus fulvestrant. The dual primary end point was investigator-assessed progression-free survival assessed both in the overall population and among patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors. Safety was assessed. RESULTS: Overall, 708 patients underwent randomization; 289 patients (40.8%) had AKT pathway alterations, and 489 (69.1%) had received a CDK4/6 inhibitor previously for advanced breast cancer. In the overall population, the median progression-free survival was 7.2 months in the capivasertib-fulvestrant group, as compared with 3.6 months in the placebo-fulvestrant group (hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.51 to 0.71; P<0.001). In the AKT pathway-altered population, the median progression-free survival was 7.3 months in the capivasertib-fulvestrant group, as compared with 3.1 months in the placebo-fulvestrant group (hazard ratio, 0.50; 95% CI, 0.38 to 0.65; P<0.001). The most frequent adverse events of grade 3 or higher in patients receiving capivasertib-fulvestrant were rash (in 12.1% of patients, vs. in 0.3% of those receiving placebo-fulvestrant) and diarrhea (in 9.3% vs. 0.3%). Adverse events leading to discontinuation were reported in 13.0% of the patients receiving capivasertib and in 2.3% of those receiving placebo. CONCLUSIONS: Capivasertib-fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone among patients with hormone receptor-positive advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor therapy with or without a CDK4/6 inhibitor. (Funded by AstraZeneca and the National Cancer Institute; CAPItello-291 ClinicalTrials.gov number, NCT04305496.).

Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer.

BACKGROUND: The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known. METHODS: We performed a prospective trial involving 9427 women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative, axillary node-negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger. RESULTS: The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95% confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95% CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95% CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5% (≤1.8±0.9%) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0% with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10% among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4%) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3%). CONCLUSIONS: Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.).

Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer.

BACKGROUND: The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score. METHODS: We performed a prospective trial involving 10,273 women with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease-free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death). RESULTS: Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease-free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P=0.26). At 9 years, the two treatment groups had similar rates of invasive disease-free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local-regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemotherapy benefit for invasive disease-free survival varied with the combination of recurrence score and age (P=0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25. CONCLUSIONS: Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger. (Funded by the National Cancer Institute and others; TAILORx ClinicalTrials.gov number, NCT00310180 .).

Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.

BACKGROUND: Prior studies with the use of a prospective-retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker. METHODS: We performed a prospective trial involving women with hormone-receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative, axillary node-negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension (or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features. A reverse-transcriptase-polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue, and the results were used to calculate a score indicating the risk of breast-cancer recurrence; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10, indicating a very low risk of recurrence (on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence). RESULTS: Of the 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease-free survival was 93.8% (95% confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3% (95% CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local-regional site was 98.7% (95% CI, 97.9 to 99.2), and the rate of overall survival was 98.0% (95% CI, 97.1 to 98.6). CONCLUSIONS: Among patients with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features, those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.).

The current situation regarding the availability and accessibility of anticancer drugs for breast cancer in the Peruvian public health systems.

The availability of effective, accessible, safe and high-quality anticancer drugs for the medical treatment of cancer is fundamental in ensuring optimal healthcare in the public health system in Peru. The main objective is to assess the current situation regarding anticancer drugs (termed 'high-cost') for breast cancer, as well as an analysis of the possible factors which negatively impact access to the Peruvian public health systems.There are similarities in the availability of anticancer drugs, since most treatments are covered by the Peruvian Ministry of Health. EsSalud offers an extra monoclonal antibody (pertuzumab) in the metastatic treatment stage. Meanwhile, the National Institute of Neoplastic Diseases (INEN), mainly for metastatic disease, has relied on more tested treatments over the last year. An agreement has been reached with the armed forces, which will enable patients to receive oncology care at the INEN and, thereby, benefit from the use of high-cost drugs.

Linfoma de células grandes T anaplásico: experiencia de 10 años en el Instituto Nacional de Enfermedades Neoplásicas, Lima - Perú / Anaplastic large T-cell lymphoma: 10-year experience at the National Institute of Neoplastic Diseases, Lima ­ Peru

Introducción: El Linfoma de Células Grandes T Anaplásico es una patología infrecuente, determinada por la expresión del CD30, con diferentes características en su presentación y ser de carácter más agresivos de acuerdo a la expresión del ALK. Objetivos: El presente estudio busca determinar las características epidemiológicas, clinicopatológicas y pronóstico de los pacientes con Linfoma de Células Grandes T Anaplásico. Métodos: Estudio descriptivo, retrospectivo de pacientes diagnosticados con Linfoma de Células Grandes T Anaplásico del Instituto Nacional de Enfermedades Neoplásicas (INEN) entre los años 2006 al 2016. Resultados: Se analizaron y revisaron la patología de 86 pacientes, 57% fueron hombres y 33% mujeres, de la población total 21,9% fueron positivos para ALK. 48 de los pacientes se encontraron en EC I y II y 36 entre estadios III y IV. 57 pacientes presentaban riesgo bajo o intermedio bajo mientras que 26 entre riesgo intermedio alto y alto. La sobrevida global estimada fue 40,8% a los 5 años, en el grupo de pacientes con ALK + fue 67,4% y en el grupo con ALK- se estimó en 30,2%. Conclusiones: El Linfoma de Células Grandes T Anaplásico es una enfermedad agresiva, con distribución heterogénea respecto a la edad y ligeramente más frecuente en varones, con el ALK y el índice pronóstico internacional como factores pronósticos importantes.

Introduction: Anaplastic Large T-Cell Lymphoma is an infrequent pathology, determined by the expression of CD30, with different characteristics in its presentation and being more aggressive according to the expression of ALK. Objectives: The present study seeks to determine the epidemiological, clinicopathological and prognostic characteristics of patients with Anaplastic Large T-Cell Lymphoma. Methods: Descriptive, retrospective study of patients diagnosed with Anaplastic Large T-Cell Lymphoma of the National Institute of Neoplastic Diseases (INEN) between 2006 and 2016. Results: The pathology of 86 patients was analyzed and reviewed, 57% were men and 33% women, of the total population 21.9% were positive for ALK. 48 of the patients were found in CD I and II and 36 between stages III and IV. 57 patients had low or low-intermediate risk, while 26 had high-intermediate and high risk. The estimated overall survival was 40.8% at 5 years, in the group of patients with ALK + it was 67.4% and in the group with ALK- it was estimated at 30.2%. Conclusions: Anaplastic Large T-Cell Lymphoma is an aggressive disease, with a heterogeneous distribution with respect to age and slightly more frequent in males, with ALK and the international prognostic index as important prognostic factors.

Características clínicas, patológicas y evolución en pacientes con cáncer de mama hereditario y esporádico en el Instituto Nacional de Enfermedades Neoplásicas / Clinical, pathological characteristics and evolution in patients with hereditary and sporadic breast cancer at the Instituto Nacional de Enfermedades Neoplasicas

Determinar las características clínicas, patológicas y evolución de pacientes con cáncer de mama hereditario y esporádico evaluados en un centro oncológico nacional. Material y métodos: Se realizó un estudio retrospectivo observacional en el Instituto Nacional de Enfermedades Neoplásicas (2009-2010) que evaluó las características clínicas, patológicas y sobrevida de 95 pacientes con cáncer de mama esporádico, y 59 casos con patrón hereditario diagnosticados en base a la historia familiar por el servicio de Genética. Resultados: La media de edad fue significativamente menor en los casos hereditarios que los esporádicos (53,5 vs. 44,8 años; p<0.001). Las pacientes con cáncer esporádico fueron diagnosticadas en estadios clínicos más avanzados debido a diferencias significativas en el tamaño tumoral. El fenotipo triple negativo fue más frecuente en los casos con patrón hereditario que los esporádicos (44.1 vs. 28.9%; p=0.036). La indicación de quimioterapia neoadyuvante fue significativamente mayor en el grupo esporádico. Las tasas de sobrevida libre de enfermedad y sobrevida global no alcanzaron significancia estadística. Conclusiones: Los casos de cáncer de mama hereditario presentan con mayor frecuencia fenotipo triple negativo y son diagnosticados a menor edad en promedio que los esporádicos. Las tasas de sobrevida global y sobrevida libre de enfermedad fueron similares entre ambos grupos.

Describe the clinicopathological characteristics and outcome in patients with hereditary and sporadic breast cancer selected from a national cancer center. Material and methods: We conducted a retrospective observational study at the Instituto Nacional de Enfermedades Neoplásicas (2009-2010), including 95 sporadic and 59 hereditary breast cancer patients. They were diagnosed on basis of their family history by the Department of Genetics. Results: The median age at diagnosis of hereditary cases were significant lower than sporadic (53,5 vs. 44,8 years; p=<0.001). Sporadic cancer patients were diagnosed at more advanced stage mainly because of an increased tumor size. Triple-negative cases were statistically more common in the hereditary than sporadic group (44.1 vs. 28.9%; p=0.036). Indication for neoadjuvant chemotherapy was more frecuent in sporadic cases. Overall survival and disease-free survival did not reach statistical significance. Conclusions: Hereditay breast cancer tumors preferentially show a triple negative phenotype and patients are diagnosed at younger age than sporadic cases. Overall survival and disease-free survival were both similar between the two groups.

Hipercalcemia asociada a leucemia mieloide aguda. Reporte de un caso y revisión de la literatura / Associated hypercalcemia to acute myeloid leukemia. Case report and literature review

Hipercalcemia es una rara pero bien reconocida complicación en leucemia mieloide aguda (LMA). Nosotros estudiamos el caso de un paciente con LMA con 46 por ciento de monocitos en el aspirado de médula ósea y un cariotipo - 7, complicada con hipercalcemia y compromiso renal. Se presenta una breve revisión de la literatura acerca de esta asociación.

Linfoma maligno en ancianos diferencias en la selección y evolución de pacientes / Malignant lymphoma in elders differentiates in the selection and evolution of patient

Objetivo: Comparación de las características de la enfermedad, respuesta a tratamiento y sobrevida en pacientes mayores de 60 años portadores de Linfoma Maligno seleccionados para ensayos clínicos vs no seleccionados. Pacientes y Métodos: pacientes portadores de Linfoma Maligno diagnósticados en diciembre de 1993 y Junio 1994 seleccionados para protocolos de investigación, pacientes diagnosticados de Linfoma Maligno en Diciembre de 1993 a Junio 1994 no seleccionados para protocolo y un grupo de control histórico diagnosticado entre 1990 y 1993. Resultados: El análisis del tiempo libre de enfermedad entre pacientes seleccionados para protocolo fue significativa con un 70 por ciento a los 5 años y un 55 por ciento a los 10 años vs 30 por ciento a los 5 años y 20 años a los 10 años en aquellos pacientes no seleccionados para ensayos clínicos. El estudio comparativo de las características de la enfermedad y respuesta a tratamiento no fueron significativos. Conclusiones: Un adecuado estudio diagnóstico y un seguimiento sistemático contribuye a tener un mayor tiempo libre de enfermedad en pacientes portadores de Linforma Maligno mayores de 60 años: Las características de la enfermedad no constituyen un factor pronóstico significativo en este estudio.

Tratamiento ambulatorio de pacientes con neutropenia febril de bajo riesgo de acuerdo al índice de riesgo MASCC / Ambulatory treatment of patient with neutropenia feverish of under risk according to the index of risk MASCC

La neutropenia febril (NF) es una complicación potencialmente letal del tratamiento citotóxico del cáncer. Ocurre prácticamente después de cualquier régimen de quimioterapia. Aún no está claro el perfil del paciente en riesgo de NF tras recibir quimioterapia. Se evaluaron 60 pacientes en forma prospectiva tomando cuentas hemáticas completas los días 1,5 y 15, en busca de la relación entre la linfopenia del día 5(precoz) de quimioterapia con el riesgo de desarrollar NF. En el análisis univariado se determinó que la linfopenia precoz tiene correlación estadística con el desarrollo de NF(p=0,004); en el análisis multivariado se identificó que el valor de hemoglobina por debajo de 110g/L en la mujer y menor de 130g/L en el varón constituyen un factor de riesgo independiente para el desarrollo de NF (p=0,012) con un odds ratio de 0,2. Finalmente podemos concluir que el hemograma del día 5 puede constituir una herramienta importante en el diseño del perfil de riesgo de NF y que el valor de hemoglobina inferior a los niveles ideales refleja el grado de toxicidad medular y constituye un factor de riesgo para desarrollar NF; permitiendo al oncólogo médico seleccionar pacientes que podrían beneficiarse con tratamiento profiláctico.