Biosimilar Use in Breast Cancer Treatment: A National Survey of Brazilian Oncologists' Opinions, Practices, and Concerns.

PURPOSE: Breast cancer is the most common malignancy in Brazilian women, with 66,280 new cases in 2020 (with 20% overexpressing human epidermal growth factor receptor 2 [HER2]). The trastuzumab biosimilar was the first oncology biosimilar approved in Brazil for HER2-positive breast cancer treatment. This study aimed to assess the current level of knowledge of biosimilars, comfort of use, extrapolation indications, and switching of practices among oncologists in Brazil. METHODS: A 24-question survey was developed using an online platform that sought information regarding responders' characteristics and use of biosimilars. The survey analyzed the basic knowledge of biosimilars, trastuzumab biosimilars, level of comfort with extrapolation, switching treatment regimens, and opinions concerning the cost of HER2-positive breast cancer therapy. Data were collected between July and September 2019 and included 144 oncologists from five Brazilian regions. RESULTS: In total, 95% of respondents could identify the most appropriate definition of biosimilars and 96% felt comfortable prescribing trastuzumab biosimilars. Although 63% of respondents would use the biosimilar in all settings wherein the reference biologic was approved, 35% would use the biosimilar for cases involving metastatic disease. Although 82% of oncologists were in favor of switching from a reference biologic to a biosimilar, 18% would avoid switching regimens. The lack of studies detailing switching to other regimens and the correct timing to switch was the major concern. The cost of HER2 therapy was a significant concern for most oncologists. CONCLUSION: Oncologists demonstrated a high level of knowledge of biosimilars and encouraging levels of prescriber use; however, extrapolation and switching treatment regimens are barriers to the effective use of biosimilars in cancer treatment. Efforts should be concentrated on strategies involving medical education programs on biosimilars.

Axillary management for patients with breast cancer after neoadjuvant chemotherapy: Results of a survey among Brazilian breast surgeons.

BACKGROUND: Currently, there are broadly differing patterns in the management of the axilla after neoadjuvant chemotherapy (NAC) and no consensus with clinically strong evidence on the subject. A survey was performed to assess the current axillary management after NAC among Brazilian breast cancer surgeons. METHODS: The Brazilian Society of Mastology members were invited by email to complete an anonymous online survey and a total of 426 responses were collected. RESULTS: The majority of responders (67%) indicated performing routine axillary staging by physical exam, ultrasound, and fine needle biopsy in case of a suspicious node before NAC. Among breast surgeons working in the Brazilian Public Unified Health System, 11.3% answered that sentinel lymph node biopsy (SLNB) is not reasonable after NAC in their services. Seventy-seven responders (18.2%) reported performing SLNB instead of axillary lymph node dissection (ALND) only in patients who are clinically node-negative before NAC. Axillary complete pathologic response is necessary to omit ALND for 42.8% of responders. The molecular profile of a breast tumor is not considered when choosing axillary management after NAC for 73.7% of responders. CONCLUSIONS: Our survey highlighted the trend towards de-escalation of axillary surgery and observed high heterogeneity in axillary management after chemotherapy in a group of brazilian breast surgeons.

Combination chemotherapy versus single-agent chemotherapy during preoperative chemoradiation for resectable rectal cancer.

BACKGROUND: Colorectal cancer represents 10% of all cancers and is the third most common cause of death in women and men. Almost two-thirds of all bowel cancers are cancers of the colon and over one-third (34%) are cancers of the rectum, including the anus. Surgery is the cornerstone for curative treatment of rectal cancer. Mesorectal excision decreases the rate of local recurrences; however, it does not improve the overall survival of people with locally advanced rectal cancer. There have been significant research efforts since the mid-1990s to optimise the treatment of rectal cancer. Based on the findings of clinical trials, people with T3/T4 or N+ rectal tumours are now being treated preoperatively with radiation and chemotherapy, mainly fluoropyrimidine. However, the incidence of distant metastases remains as high as 30%. Combination chemotherapy regimens, similar to those used in metastatic disease with the addition of oxaliplatin and irinotecan, have been tested to improve the prognosis of people with rectal cancer. OBJECTIVES: To compare outcomes (including overall survival, disease-free survival and toxicity) between two 5-fluorouracil-containing chemotherapy regimens in people with stage II and III rectal cancer who are receiving preoperative chemoradiation. SEARCH METHODS: We searched the Cochrane Colorectal Cancer Group Specialised Register (January 2015), the Cochrane Central Register of Controlled Trials (2015, Issue 1), Ovid MEDLINE (1950 to January 2015), Ovid EMBASE (1974 to January 2015) and LILACS (1982 to January 2015). We reviewed the reference lists of included studies, checked clinical trials registers and handsearched relevant journal proceedings. We applied no language or publication restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing single-agent chemotherapy (fluoropyrimidine) versus combination chemotherapy (fluoropyrimidine plus another agent including, but not limited to, oxaliplatin) during preoperative radiochemotherapy in people with resectable rectal cancer. DATA COLLECTION AND ANALYSIS: Two review authors (HMR, EMKS) independently extracted data and assessed trial quality. When necessary, we requested additional information and clarification of published data from the authors of individual trials. MAIN RESULTS: We included four RCTs involving 3875 people with resectable rectal cancer. In the preoperative period, the participants of these studies were randomised to receive chemoradiation either with a single fluoropyrimidine agent (capecitabine or 5-fluorouracil) or with a combination of drugs (fluoropyrimidine plus oxaliplatin). The only study that reported overall survival and disease-free survival found no significant differences between the intervention and control groups; we considered this evidence very low quality. For pathological complete response after preoperative treatment (ypCR) there was high quality evidence favouring the intervention group (odds ratio (OR) 1.23, 95% confidence interval (CI) 1.04 to 1.46), but there was also moderate quality evidence suggesting a higher risk for early toxicity in the intervention group (OR 2.07, 95% CI 1.31 to 3.27). Moderate to high quality evidence suggested that the control group had better compliance to radiotherapy (OR 0.32, 95% CI 0.14 to 0.75). There were no significant differences between groups in postoperative mortality within 60 days, postoperative morbidity, resection margins, abdominoperineal resection and Hartmann procedures. AUTHORS' CONCLUSIONS: There was very low quality evidence that people with resectable rectal cancer who receive combination preoperative chemotherapy have no improvements in overall survival or disease-free survival. There was high quality evidence that suggested that combination chemotherapy with oxaliplatin may improve local tumour control in people with resectable rectal cancer, but this regimen also caused more toxicity. The review included four RCTs but only one reported survival; therefore, we cannot make robust conclusions or useful clinical recommendations. The publication of more survival data from these studies will contribute to future analyses.

ANTECEDENTES: El cáncer colorrectal representa el 10% de todos los cánceres y es la tercera causa más frecuente de muerte en mujeres y hombres. Casi dos tercios de todos los cánceres intestinales son cánceres de colon y más de un tercio (34%) son cánceres del recto, incluido el ano. La cirugía es la base del tratamiento curativo del cáncer rectal. La escisión mesorrectal disminuye la tasa de recidivas locales; sin embargo, no mejora la supervivencia general de las personas con cáncer de recto localmente avanzado. Desde mediados de los años noventa se han realizado esfuerzos significativos de investigación para optimizar el tratamiento del cáncer rectal. Según los resultados de los ensayos clínicos, actualmente las personas con tumores rectales T3/T4 o N+ se tratan preoperatoriamente con radiación y quimioterapia, principalmente fluoropirimidina. Sin embargo, la incidencia de metástasis distantes todavía es tan alta como del 30%. Para mejorar el pronóstico de las personas con cáncer rectal se han probado regímenes de quimioterapia combinada, similares a los utilizados en la enfermedad metastásica con el agregado de oxaliplatino e irinotecán. OBJETIVOS: Comparar los desenlaces (incluida la supervivencia general, la supervivencia sin enfermedad y la toxicidad) entre dos regímenes de quimioterapia que contienen 5­fluorouracilo en personas con cáncer rectal estadio II y III que reciben quimiorradioterapia preoperatoria. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en el Registro especializado del Grupo Cochrane Colorrectal (Cochrane Colorectal Cancer Group) (enero de 2015), Registro Cochrane central de ensayos controlados (Cochrane Central Register of Controlled Trials) (2015, número 1), Ovid MEDLINE (1950 hasta enero de 2015), Ovid EMBASE (1974 hasta enero de 2015) y en LILACS (1982 hasta enero de 2015). Se revisaron las listas de referencias de los estudios incluidos, se verificaron los registros de ensayos clínicos y se hicieron búsquedas manuales en los resúmenes de revistas relevantes. No se aplicaron restricciones de idioma ni de publicación. CRITERIOS DE SELECCIÓN: Ensayos controlados aleatorizados (ECA) que compararon la quimioterapia de agente único (fluoropirimidina) versus la quimioterapia combinada (fluoropirimidina más otro agente que incluyó, pero no se limitó a oxaliplatino) durante la radioquimioterapia preoperatoria en personas con cáncer rectal resecable. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión (HMR, EMKS) de forma independiente extrajeron los datos y evaluaron la calidad de los ensayos. Cuando fue necesario, se solicitó información adicional y aclaraciones sobre los datos publicados de los autores de los ensayos individuales. RESULTADOS PRINCIPALES: Se incluyeron cuatro ECA con 3875 personas con cáncer rectal resecable. En el período preoperatorio, los participantes de estos estudios se asignaron al azar a recibir quimiorradioterapia con el agente único fluoropirimidina (capecitabina o 5­fluorouracilo) o con una combinación de fármacos (fluoropirimidina más oxaliplatino). El único estudio que informó sobre la supervivencia general y la supervivencia sin enfermedad no encontró diferencias significativas entre los grupos de intervención y control; esta evidencia se consideró de calidad muy baja. Para la respuesta patológica completa después del tratamiento preoperatorio (ypCR) hubo evidencia de calidad alta a favor del grupo de intervención (odds ratio [OR] 1,23; intervalo de confianza [IC] del 95%: 1,04 a 1,46), pero también hubo evidencia de calidad moderada que indicó un mayor riesgo de toxicidad temprana en el grupo de intervención (OR 2,07; IC del 95%: 1,31 a 3,27). Evidencia de calidad moderada a alta indicó que el grupo control tuvo un mejor cumplimiento de la radioterapia (OR 0,32; IC del 95%: 0,14 a 0,75). No hubo diferencias significativas entre los grupos en la mortalidad posoperatoria en el transcurso de 60 días, la morbilidad posoperatoria, los márgenes de resección, la resección abdominoperineal ni los procedimientos de Hartmann. CONCLUSIONES DE LOS AUTORES: Hubo evidencia de calidad muy baja de que las personas con cáncer rectal resecable que reciben quimioterapia combinada preoperatoria no tienen mejorías en la supervivencia general ni la supervivencia sin enfermedad. Hubo evidencia de calidad alta que indicó que la quimioterapia combinada con oxaliplatino podría mejorar el control tumoral local en las personas con cáncer rectal resecable, pero este régimen también provocó más toxicidad. La revisión incluyó cuatro ECA, pero sólo uno informó sobre la supervivencia; por lo tanto, no se pueden establecer conclusiones sólidas ni recomendaciones clínicas útiles. La publicación de más datos de la supervivencia de estos estudios contribuirá a futuros análisis.