Real-World Evidence of Ribociclib Plus Aromatase Inhibitors as First-Line Treatment in Advanced Breast Cancer: The BrasiLEEira Study.

PURPOSE: Cyclin inhibitors plus endocrine therapy represent the reference standard for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer (ABC). Efficacy results on hard end points such as overall survival come from well-designed randomized clinical trials (RCTs). However, a limitation of RCTs is the low external results validity, and their extrapolation to a broader population may not be appropriate. Real-world studies can overcome these limitations, also increasing the reliability of RCTs. MATERIALS AND METHODS: The BrasiLEEira was an observational, longitudinal, retrospective, multicenter study to evaluate the effectiveness and safety of ribociclib plus nonsteroidal aromatase inhibitors in Brazilian women age 18 years or older with HR+/HER2- ABC. The study was approved by the institutional review boards of all 11 hospitals. Data were collected anonymously from medical records using an electronic case report form designed by an independent academic research organization, which conducted the study considering all recommendations of international guidelines. The primary end point was 1-year progression-free survival (PFS) rate. Secondary end points included mortality, dose reduction, and safety. RESULTS: The mean age of 76 patients was 57 years, and 28.9% were Black/Brown. The most prevalent comorbidity was arterial hypertension (34.7%). About 26.0% had endocrine-resistant disease, and 54.1% had more than three metastatic sites. The PFS rate was 77.6%. Three patients died (3.9%). Dose reductions occurred in 37.7% of patients. The most common adverse event was neutropenia (68.4%). CONCLUSION: The high-quality evidence from the BrasiLEEira study corroborates the RCTs' findings, expanding its validity to a broader spectrum and underrepresented population who may benefit from ribociclib treatment.

Breast and gynecologic cancers as a Brazilian health priority.

OBJECTIVE: Cancer imposes a profound burden on low- and middle-income countries where 65% of the global cancer deaths occurred in 2020. The objective of the present review was to describe female cancer epidemiology in Brazil, barriers to prevention, screening, and treatment, and to propose strategies to a better control. METHODS: For the process of literature search and scientific acquisition, we have utilized the terms "female cancer" AND "breast cancer," AND "cervical cancer" AND "endometrial cancer" AND "ovarian cancer" AND "Brazil" in PubMed. References of the articles included in this review were manually searched in order to identify relevant studies on the topic. The official Brazilian epidemiology data were extensively analyzed at the governmental site www.inca.gov.br. RESULTS: Considering cases of breast and gynecologic cancers together, 105,770 new cases are expected to be diagnosed yearly, positioning female cancer as the highest cancer incidence in Brazil. Female breast cancer is the most common and the leading cause of death from cancer in the female population in all regions of Brazil, except in the North, where cervical cancer ranks first. Cervical cancer, a preventable disease, corresponds to the third-most common neoplasia in women, with higher incidences in the North and Northeast regions of Brazil. An upward trend has been observed in endometrial cancer incidence, a tendency that follows the increase of its two most common risk factors: population aging and obesity. Ovarian cancer currently occupies the eighth position among female cancers in Brazil, but it is the most lethal gynecologic cancer. The main strategies to reduce female cancer mortality rates are the reduction of inequalities in healthcare services and the early diagnosis of cases. The lack of a specific national cancer program results in a reactive and unplanned approach to healthcare provision, ultimately leading to suboptimal resource utilization and higher expenditure. CONCLUSION: Analyzed together, breast and gynecologic cancers correspond to the leading cause of cancer in Brazil. A heterogeneous group, female cancer includes diseases with a high primary and secondary prevention potential. The organization of a female cancer program in Brazil prioritizing primary and secondary prevention strategies, such as adequate mammography screening and human papillomavirus vaccination coverage, could significantly improve female cancer control in the country.

Real-world treatment outcomes in HR+ HER2- metastatic breast cancer patients treated with CDK4/6 inhibitors: Results from a reference center in Brazil.

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have been recently developed and introduced into clinical practice. METHODS: We retrospectively analyzed data from patients with confirmed HR+/HER2 metastatic breast cancer treated with hormonal therapy in combination with ribociclib (R), palbociclib (P), or abemaciclib (A). OUTCOMES: median progression-free survival (mPFS), time to treatment discontinuation (mTTD), and objective response rate (ORR). RESULTS: Between January 2016 - June 2021, 142 patients were treated with an CDK4/6i (79 P, 42 R, 21 A). The median age was 59 years and 67.6% had recurrent disease. Roughly 35.2%, 36.6%, 28.2% of the patients had 1, 2 or 3+ metastatic sites, respectively, and 55.6% of the patients received CDK4/6i as a first-line treatment. The mPFS was 28m(R) vs. 14m(P) vs. 6m(A) (P = 0.002), with a higher proportion of patients receiving R in the first-line setting. However, no difference was seen when the analysis was restricted to the first-line scenario (P = 0.193). Sixty-four patients required one dose reduction, and 19 patients required two. ORR was 76.2% (R) vs 62% (P) vs 42.9% (A). More patients achieved a complete response with R and P, with no difference in the incidence of partial response and stable disease. Adverse events occurred in 94.4% of the population, with the most common grade 3-4 AE being neutropenia (59.1%). CONCLUSIONS: Our results confirm the efficacy and tolerability of CDK4/6i in routine clinical practice. This is the first real-world data describing and comparing the efficacy and toxicity of CDK4/6i in the Brazilian population.

Breast and gynecologic cancers as a Brazilian health priority

SUMMARY OBJECTIVE: Cancer imposes a profound burden on low- and middle-income countries where 65% of the global cancer deaths occurred in 2020. The objective of the present review was to describe female cancer epidemiology in Brazil, barriers to prevention, screening, and treatment, and to propose strategies to a better control. METHODS: For the process of literature search and scientific acquisition, we have utilized the terms "female cancer" AND "breast cancer," AND "cervical cancer" AND "endometrial cancer" AND "ovarian cancer" AND "Brazil" in PubMed. References of the articles included in this review were manually searched in order to identify relevant studies on the topic. The official Brazilian epidemiology data were extensively analyzed at the governmental site www.inca.gov.br. RESULTS: Considering cases of breast and gynecologic cancers together, 105,770 new cases are expected to be diagnosed yearly, positioning female cancer as the highest cancer incidence in Brazil. Female breast cancer is the most common and the leading cause of death from cancer in the female population in all regions of Brazil, except in the North, where cervical cancer ranks first. Cervical cancer, a preventable disease, corresponds to the third-most common neoplasia in women, with higher incidences in the North and Northeast regions of Brazil. An upward trend has been observed in endometrial cancer incidence, a tendency that follows the increase of its two most common risk factors: population aging and obesity. Ovarian cancer currently occupies the eighth position among female cancers in Brazil, but it is the most lethal gynecologic cancer. The main strategies to reduce female cancer mortality rates are the reduction of inequalities in healthcare services and the early diagnosis of cases. The lack of a specific national cancer program results in a reactive and unplanned approach to healthcare provision, ultimately leading to suboptimal resource utilization and higher expenditure. CONCLUSION: Analyzed together, breast and gynecologic cancers correspond to the leading cause of cancer in Brazil. A heterogeneous group, female cancer includes diseases with a high primary and secondary prevention potential. The organization of a female cancer program in Brazil prioritizing primary and secondary prevention strategies, such as adequate mammography screening and human papillomavirus vaccination coverage, could significantly improve female cancer control in the country.

What can we learn from more than 1,000 Brazilian patients at risk of hereditary cancer?

Background: Identifying individuals at a higher risk of developing cancer is a major concern for healthcare providers. Cancer predisposition syndromes are the underlying cause of cancer aggregation and young-onset tumors in many families. Germline genetic testing is underused due to lack of access, but Brazilian germline data associated with cancer predisposition syndromes are needed. Methods: Medical records of patients referred for genetic counseling at the Oncogenetics Department at the Hospital Sírio-Libanês (Brasília, DF, Brazil) from July 2017 to January 2021 were reviewed. The clinical features and germline findings were described. Detection rates of germline pathogenic/likely pathogenic variant (P/LPV) carriers were compared between international and Brazilian guidelines for genetic testing. Results: A total of 1,091 individuals from 985 families were included in this study. Most patients (93.5%) had a family history of cancer, including 64% with a family member under 50 with cancer. Sixty-six percent of patients (720/1091) had a personal history of cancer. Young-onset cancers (<50 years old) represented 62% of the patients affected by cancer and 17% had multiple primary cancers. The cohort included patients with 30 different cancer types. Breast cancer was the most prevalent type of cancer (52.6%). Germline testing included multigene panel (89.3%) and family variant testing (8.9%). Approximately 27% (236/879) of the tested patients harbored germline P/LPVs in cancer susceptibility genes. BRCA2, BRCA1, and TP53 were the most frequently reported genes, corresponding to 18.6%, 14.4%, and 13.5% of the positive results, respectively. Genetic testing criteria from international guidelines were more effective in identifying carriers than the Brazilian National Agency of Supplementary Health (ANS) criteria (92% vs. 72%, p<0.001). Forty-six percent of the cancer-unaffected patients who harbored a germline P/LPV (45/98) would not be eligible for genetic testing according to ANS because they did not have a family variant previously identified in a cancer-affected relative. Conclusion: The high detection rate of P/LPVs in the present study is possibly related to the genetic testing approach with multigene panels and cohort's characteristics, represented mainly by individuals with a personal or family history of young-onset cancer. Testing asymptomatic individuals with suspicious family history may also have contributed to a higher detection rate. A significant number of carriers would not have been identified using ANS criteria for genetic testing.