RESUMO
BACKGROUND: Breast cancer (BC) incidence increases with age, particularly in HR-positive/HER2-negative subtypes. Cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6is) alongside endocrine therapy (ET) have emerged as promising treatments for HR-positive/HER2-negative advanced and early BC. However, their efficacy, safety, and impact on quality of life (QoL) in older and frail patients remain underexplored. METHODS: This position paper assesses the existing literature from 2015 to 2024, focusing on CDK4/6is use in patients aged 65 years and older with HR-positive/HER2-negative BC. RESULTS: Our analysis methodically addresses critical questions regarding the utilization of CDK4/6is in the elderly BC patient population, organizing findings from the metastatic and adjuvant settings. In the metastatic setting, CDK4/6is significantly improve progression-free survival (PFS), paralleling benefits observed in younger patients, and suggest potential overall survival (OS) benefits, warranting further investigation. Despite an increased incidence of grade ≥ 3 adverse events (AEs), such as neutropenia and asthenia, CDK4/6is present a markedly lower toxicity profile compared to traditional chemotherapy, with manageable side effects. QoL analysis indicates that integrating CDK4/6is into treatment regimens does not significantly impact elderly BC patients' daily life and symptom management. Special attention is given to frail subgroups, and personalized approaches are recommended to balance efficacy and adverse effects, such as starting with ET alone and introducing CDK4/6is upon progression in patients with a low disease burden. Transitioning to the adjuvant setting, early results, particularly with abemaciclib, indicate positive effects on disease-free survival (DFS), emphasizing the need for continued analysis to validate these findings and assess long-term implications. However, data on older patients are insufficient to conclude whether they truly benefit from this treatment. CONCLUSION: Overall, CDK4/6is present a favorable benefit-risk profile in older BC patients, at least in advanced BC; however, further research is warranted to optimize treatment strategies and improve outcomes in this population.
RESUMO
PURPOSE: Metastatic renal cell carcinoma (mRCC) still harbours a big propensity for future metastasis. Combinations of immune and targeted therapies are currently the cornerstone of management with a less clear role for surgical metastasectomy (SM). METHODS: We performed a narrative review of literature searching for the available evidence on the yield of surgical metastasectomy in the era of targeted and immune therapies. The review consisted of a PubMed search of relevant articles using the Mesh terms:" renal cell carcinoma", "surgery¼, «resection", "metastasectomy", "molecular targeted therapies", "immune checkpoint inhibitors" alone or in combination. RESULTS: In this review, we exposed the place of surgical metastasectomy within a multimodal treatment algorithm for mRCC Also, we detailed the patient selection criteria that yielded the best results when SM was performed. Finally, we discussed the feasibility and advantages of SM per organ site. CONCLUSION: Our work was able to show that SM could be proposed as a consolidation treatment to excise residual lesions that were deemed unresectable prior to a combination of systemic therapies. Contrastingly, it can be proposed as an upfront treatment, leaving systemic therapies as an alternative in case of future relapse. However, patient selection regarding their performance status, metastatic sites, number of lesions and tumorous characteristics is of paramount importance.