Prospective, multicenter study on the economic and clinical impact of gene-expression assays in early-stage breast cancer from a single region: the PREGECAM registry experience.

INTRODUCTION: The aim of this study is to evaluate the cost-effectiveness and impact of gene-expression assays (GEAs) on treatment decisions in a real-world setting of early-stage breast cancer (ESBC) patients. METHODS: This is a regional, prospective study promoted by the Council Health Authorities in Madrid. Enrolment was offered to women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, node-negative or micrometastatic, stage I or II breast cancer from 21 hospitals in Madrid. Treatment recommendations were recorded before and after knowledge of tests results. An economic model compared the cost-effectiveness of treatment, guided by GEAs or by common prognostic factors. RESULTS: 907 tests (440 Oncotype DX® and 467 MammaPrint®) were performed between February 2012 and November 2014. Treatment recommendation changed in 42.6% of patients. The shift was predominantly from chemohormonal (CHT) to hormonal therapy (HT) alone, in 30.5% of patients. GEAs increased patients' confidence in treatment decision making. Tumor grade, progesterone receptor positivity and Ki67 expression were associated with the likelihood of change from CHT to HT (P < 0.001) and from HT to CHT (P < 0.001). Compared with current clinical practice genomic testing increased quality-adjusted life years by 0.00787 per patient and was cost-saving from a national health care system (by 13.867€ per patient) and from a societal perspective (by 32.678€ per patient). CONCLUSION: Using GEAs to guide adjuvant therapy in ESBC is cost-effective in Spain and has a significant impact on treatment decisions.

Adjuvant hormonal therapy in perimenopausal patients.

This section considers the treatment options for perimenopausal women with breast cancer. The perimenopause period begins in the so-called stage 2 of menopausal transition (early menopausal transition, where the length of the cycles changes by 7 days or more) and ends after 12 months of amenorrhea. It is characterized by an early increase in follicle-stimulating hormone and is associated with the presence of anovulatory cycles, irregular periods, and loss of menstrual cycles. The recommended treatment is tamoxifen (TAM) with or without ovarian ablation for 2 or 3 years followed by a re-evaluation. TAM should be maintained if the patient is premenopausal and aromatase inhibitors (AI) are recommended once the menopausal status is confirmed. Ovarian suppression is an acceptable adjuvant therapy in those patients with hormone-sensitive tumors. AI should only be used in postmenopausal women or in combination with chemical castration in premenopausal women. This supplement paper includes the key points of roundtable presentations and discussions of hormonal therapy in breast cancer.

[Effectivity of cetuximab monotherapy in the treatment of refractory advanced cancer of the head and neck]. / Efectividad de Cetuximab en monoterapia en el tratamiento de cánceres de cabeza y cuello avanzado refractario.

INTRODUCTION: More than 90% of carcinoma of the head and neck (CHN) have an overexpression of the EGFR gene, and that overexpression is associated with a worse prognosis. Cetuximab is a monoclonal antibody against EGFR. PATIENTS AND METHODS: We have conducted a retrospective study of 10 consecutive cases with metastatic and/or recurrent CHN treated with cetuximab monotherapy as second line therapy, with the main objective of analyzing the progression-free survival (PFS); we also analyzed the response rate, the overall survival (OS), and toxicity profile as second end points. RESULTS: The median age was 55 years, and 100% of patients were males. Fourty percent of the patients received cetuximab as second line, and 60% as third line therapy. With a median follow-up of 13.5 months, the median PFS was 4 months (95%CI: 3.4-4.6 months), with a median OS of 9.7 months (95%CI: 2.9-16.6 months).The objective response rate was 10%, and the disease control rate was 60% (Partial response = 10% and stable disease for > 16 weeks = 50%). Thirty percent of patients had grade 3 rash. CONCLUSIONS: Cetuximab monotherapy has a modest effectivity in the treatment of refractory CHN, but with a limited toxicity. Future studies should use combinations of cetuximab with others effective chemotherapeutic drugs in the treatment of CHN, such as taxanes.

[Efficiency of bortezomib and dexamethasone in relapsed multiple myeloma treatment: retrospective study in consecutive cases]. / Efectividad de bortezomib y dexametasona en el tratamiento de mieloma múltiple refractario: estudio retrospectivo de una serie de casos consecutivos.

INTRODUCTION: Multiple myeloma (MM) is a plasm-cell neoplasm, that is characterized by a monoclonal protein in the serum or urine. Bortezomib is an efficacy drug for the second line treatment of MM. PATIENTS AND METHOD: We conducted a retrospective study of 21 consecutive cases with refractory MM treated with bortezomib and dexamethasone as second line therapy, with the objective of analyzing the overall response rate (primary end point), the progression-free survival (PFS), the overall survival (OS), the duration of response (DR) and toxicity profile (second end points). RESULTS: In our study we found an overall response rate of 70%. With a median follow-up of 15 months, we had a median PFS of 12 months (95% CI: 2-21 months), with a median OS of 17 months (95% CI: 2-32 months), and a median DR of 9 months (95% CI: 5-13 months). Fourty-seven percent of patients had neuropathy, the 33% thrombocytopenia, 13.33% anemia and 26.66% diarrhea. CONCLUSIONS: The combination of bortezomib and dexamethasone is an effective and safe treatment in second line of refractory MM, with a manageable toxicity.

[Adjuvant treatment of operable breast cancer]. / Tratamiento adyuvante en el cáncer de mama operable.

Breast cancer(BC) is the most frequent neoplasm in women of the west countries. The treatment of BC is very complex, and include the combination of surgery, chemotherapy, radiotherapy, hormone therapy and immunotherapy. Surgery is the gold standard in the radical treatment of BC. Anthracyclines and taxanes are very important in the adjuvant treatment of BC. These drugs have shown an increased disease-free-survival and overall survival in several studies. Tamoxifen has been the gold standard adjuvant hormone therapy for the treatment of postmenopausal women with hormone-receptor-positive early BC for many years, but the third-generation aromatase inhibitors (letrozole, anastrozole, and exemestane) are now recommended as the preferred therapy. Trastuzumab in combination with adjuvant chemotherapy has changed the natural history of early Her-2 positive BC. New drugs are under investigation in the treatment of BC.

Efectividad de Cetuximab en monoterapia en el tratamiento de cánceres de cabeza y cuello avanzado refractario / Effectivity of cetuximab monotherpay in the treatment of refractory advanced cancer of the head and neck

Introducción: más del 90% de los cánceres de cabeza y cuello (CCC) presentan una sobreexpresión del gen EGFR, y dicha sobreexpresión se asocia a un peor pronóstico. Cetuximab es un anticuerpo monoclonal dirigido contra EGFR. Pacientes y métodos: hemos llevado a cabo un estudio retrospectivo de una serie de 10 casos consecutivos de CCC metastáticos y/o recurrentes a los que hemos tratado con cetuximab en monoterapia en segundas líneas de tratamiento, con el objetivo principal de analizar la supervivencialibre de progresión (SLP), así como la tasa de respuestas, la supervivencia global (SG) y la toxicidad como objetivos secundarios. Resultados: la mediana de edad fue de 55 años, y el 100% de los pacientes eran varones. El 40% de los pacientes recibió cetuximab en segunda línea, y el 60% en tercera línea de tratamiento. Con una mediana de seguimiento de 13,5 meses, la mediana de SLP fue de 4 meses (IC95%: 3,4-4,6 meses), y la mediana de SG de 9,7 meses (IC95%: 2,9-16,6 meses). La tasa de respuestas objetivas fue del 10%, y la tasa de beneficio clínico fue del 60% (Remisión parcial = 10% y estabilización >16 semanas = 50%). El 30% de los pacientes presentaron toxicidad cutánea grado 3.Conclusiones: cetuximab en monoterapia tiene una efectividad discreta en el tratamiento de CCC refractarios, pero con una toxicidad escasa.Los futuros estudios deberían de encaminarse hacia la combinación de cetuximab con otros agentes quimioterápicos eficaces en el tratamiento de CCC, como los taxanos

Introduction: More than 90% of carcinoma of the head and neck (CHN) have an over expression of the EGFR gene, and that over expressionis associated with a worse prognosis. Cetuximab is a monoclonal antibody against EGFR. Patients and methods: We have conducted a retrospective study of 10 consecutive cases with metastatic and/or recurrent CHN treated with cetuximab monotherapy as second line therapy, with the main objective of analyzing the progression-free survival (PFS); we also analyzed there sponse rate, the overall survival (OS), and toxicity profile as secondend points. Results: The median age was 55 years, and 100% of patients were males. Fourty percent of the patients received cetuximab as second line, and 60% as third line therapy. With a median follow-up of 13.5 months, the median PFS was 4 months (95%CI: 3.4-4.6 months), with a median OS of 9.7 months (95%CI: 2.9-16.6 months).The objective response rate was 10%, and the disease control rate was 60% (Partial response = 10% and stable disease for > 16 weeks = 50%). Thirty percent of patients had grade 3 rash. Conclusions: Cetuximab monotherapy has a modest effectivity in the treatment of refractory CHN, but with a limited toxicity. Future studies should use combinations of cetuximab with others effective chemotherapeutic drugs in the treatment of CHN, such as taxanes

Efectividad de bortezomib y dexametasona en el tratamiento de mieloma múltiple refractario: estudio retrospectivo de una serie de casos consecutivos / Efficiency of Bortemozib and dexamethasone in relapsed multiple myeloma treatment: retrospective study in consecutive cases

Introducción: El mieloma múltiple (MM) es una neoplasia de células plasmáticas, que se caracteriza por la presencia de una proteína monoclonal en suero u orina. Bortezomib es un fármaco eficaz en el tratamiento de segunda línea del MM. Pacientes y métodos: Hemos realizado un estudio retrospectivo de una serie de 21 casos consecutivos de MM refractario a los que hemos tratado con bortezomib y dexametasona en segundas líneas, con el objetivo de analizar la tasa de respuesta (objetivo primario), la supervivencia libre de progresión (SLP), la supervivencia global (SG), la duración de respuesta (DR) y la toxicidad (objetivos secundarios). Resultados: En nuestro estudio hemos encontrado una tasa de respuesta total de 70%. Con una mediana de seguimiento de 15 meses, hemos obtenido una mediana de SLP de 12 meses (IC95%: 2-21 meses), una mediana de SG de 17 meses (IC95%:2-32 meses) y una mediana de DR de 9 meses (IC95%: 5-13 meses). El 47 % de los pacientes presentaron neuropatía,el 33% trombocitopenia, 13,33% anemia, y 26,66% diarrea. Conclusiones: La combinación de bortezomib y dexametasona es un tratamiento efectivo y seguro en segundas líneas de MM refractario, con una toxicidad manejable

Introduction: Multiple myeloma (MM) is a plasm-cell neoplasm, thatis characterized by a monoclonal protein in the serum or urine. Bortezomib is an efficacy drug for the second line treatment of MM. Patients and method: We conducted a retrospective study of 21 consecutive cases with refractory MM treated with bortezomib and dexamethasone as second line therapy, with the objective of analyzing the overall response rate (primary end point), the progression-free survival (PFS), the overall survival (OS), the duration of response (DR) and toxicity profile (second end points). Results: In our study we found an overall response rate of 70%. With a median follow-up of 15 months, we had a median PFS of 12 months (95% CI: 2-21 months), with a median OS of 17 months (95% CI: 2-32 months), and a median DR of 9 months (95% CI: 5-13 months). Fourtyseven percent of patients had neuropathy, the 33% thrombocytopenia,13.33% anemia and 26.66% diarrhea. Conclusions: The combination of bortezomib and dexamethasone is an effective and safe treatment in second line of refractory MM, with amanageable toxicity

Tratamiento adyuvante en el cáncer de mama operable / Adjuvant treatment of operable breast cancer

El cáncer de mama (CM) es la neoplasia más frecuente en las mujeres de los países occidentales. El tratamiento del CM es muy complejo, e incluye la combinación de la cirugía, quimioterapia, radioterapia, hormonoterapia e inmunoterapia. La cirugía continúa siendo el “gold estándar”en el tratamiento radical de CM. Las antraciclinas y los taxanos son esenciales en el tratamiento adyuvante de CM. Estos fármacos han demostrado un incremento significativo de la supervivencia libre de enfermedad y global en múltiples estudios. El tamoxifeno ha sido el “gold estándar” en la hormonoterapia adyuvante de las mujeres posmenopáusicas con receptores hormonales positivos durante muchos años, pero los inhibidores de aromatasas de tercera generación (letrozol, anastrozol y exemestano) se han convertido en el tratamiento recomendado actualmente. Trastuzumab en combinación con la quimioterapia adyuvante ha modificado la historia natural del CM localizado Her-2 positivo. Nuevos fármacos están en investigación en el tratamiento del CM

Breast cancer (BC) is the most frequent neoplasm in women of the west countries. The treatment of BC is very complex, and include the combination of surgery, chemotherapy, radiotherapy, hormonetherapy and immunotherapy. Surgery is the gold standard in the radical treatment of BC. Anthracyclines and taxanes are very important in the adjuvant treatment of BC. These drugs have shown an increased disease free-survival and overall survival in several studies. Tamoxifen has been the gold standard adjuvant hormonetherapy for the treatment of postmenopausal women with hormone-receptor-positive early BC for many years, but the third-generation aromatase inhibitors (letrozole, anastrozole, and exemestane) are now recommended as the preferred therapy.Trastuzumab in combination with adjuvant chemotherapy has changed the natural history of early Her-2 positive BC. New drugs are underinvestigation in the treatment of BC

Management of gastric adenocarcinoma.

Gastric adenocarcinoma is the second most common cause of cancer death worldwide. The prognosis for patients with gastric adenocarcinoma depends on the stage of the disease at the time of diagnosis and treatment. Early gastric cancer, limited to the mucosa and submucosa, is best treated surgically and has a five-year survival rate of 70-95%. Surgical resection remains the primary curative treatment for localised disease. Despite this, the overall survival remains poor. The management of localised gastric adenocarcinoma is complex, and at present there is proven benefit of both preoperative chemotherapy and postoperative chemoradiotherapy. There is no standard regimen of chemotherapy for metastatic disease, although the regimen of ECF (epirubicin, cisplatin and fluorouracil) is the most used regimen, with a median survival of 7-9 months. With new regimens of chemotherapy, such as DCF (docetaxel, cisplatin and fluorouracil) or the combination of irinotecan, cisplatin and bevacizumab, the median survival has increased. Other new agents are under investigation.

Management of gastric adenocarcinoma

Gastric adenocarcinoma is the second most common cause of cancer death worldwide. The prognosis for patients with gastric adenocarcinoma depends on the stage of the disease at the time of diagnosis and treatment. Early gastric cancer, limited to the mucosa and submucosa, is best treated surgically and has a five-year survival rate of 70-95%. Surgical resection remains the primary curative treatment for localised disease. Despite this, the overall survival remains poor. The management of localised gastric adenocarcinoma is complex, and at present there is proven benefit of both preoperative chemotherapy and postoperative chemoradiotherapy. There is no standard regimen of chemotherapy for metastatic disease, although the regimen of ECF (epirubicin, cisplatin and fluorouracil) is the most used regimen, with a median survival of 7-9 months. With new regimens of chemotherapy, such as DCF (docetaxel, cisplatin and fluorouracil) or the combination of irinotecan, cisplatin and bevacizumab, the median survival has increased. Other new agents are under investigation (AU)