Seminars in oncology最新文献

The development of oral cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors, including palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for patients with hormone-receptor-positive (HR+) and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (BC). When combined with an aromatase inhibitor or fulvestrant, these agents have been approved as first-line therapy in the metastatic setting. Abemaciclib has also gained FDA approval for patients with HR-positive, HER2-negative, node-positive, early BC at high risk of recurrence. Moreover, ribociclib has recently improved disease-free survival in patients with stage II or III HR+/HER2-negative early BC. CDK4/6 inhibitors have favorable safety profiles. However, the available agents have different toxicity profiles that must be clearly discussed with the patients for optimal clinical decisions. This manuscript aims to review CDK4/6 inhibitor-related treatment-associated adverse events, identify risk factors for intolerable adverse events, and assess their safety in special patient populations such as the elderly and those with renal insufficiency. Enhanced knowledge and understanding of CDK4/6 inhibitor-related toxicities can improve treatment strategies and ultimately enhance patient care.

Background

Cancer represents a leading cause of death worldwide. Germline mutations in several genes increase the risk of developing several cancers, including cancers of the breast, ovary, pancreas, colorectum, and melanoma. An understanding of the population prevalence of pathogenic germline mutations can be helpful in the design of public health interventions, such as genetic testing, which has downstream implications for cancer screening, prevention, and treatment. While population-based studies of pathogenic germline mutations exist, most such studies have been conducted in White populations. Limited data exist regarding the prevalence of germline mutations within sub-Saharan African populations.

Materials and Methods

We identified countries defined as sub-Saharan Africa by the World Bank and conducted a scoping literature review using PubMed. For each country, we identified and summarized studies that focused on the prevalence of germline genetic mutations with sample sizes >10 and in a population directly from sub-Saharan Africa, either with or without diseases associated with the relevant genetic mutations. Studies that evaluated the prevalence of somatic or likely benign variants were excluded.

Results

Within the 48 countries in sub-Saharan Africa, we identified 34 studies which meet the inclusion criteria. Twenty studies were conducted in South Africa, Nigeria, or Burkina Faso; four countries had more than two published papers. We found that 33 of 48 countries in sub-Saharan Africa lacked any genetic studies. Notably, there has been an increase in relevant studies starting in 2020. Importantly, of the 34 studies identified, 29 included data on BRCA1 or BRCA2. Data on the prevalence of mutations contributing to familial cancer syndromes other than BRCA1 and BRCA2 was limited.

Conclusions

While some progress has been made towards understanding the prevalence of germline mutations in cancer susceptibility genes, the characterization of genetic mutations among sub-Saharan African populations remains strikingly incomplete. Given the genetic diversity in the region, there remains a great need for large-scale, population-based studies to understand the prevalence of germline pathogenic mutations and adequately capture all the subpopulations in this part of the world.

Immune checkpoint inhibitors (ICI) have become a cornerstone in medical oncology, continually evolving therapeutic strategies and applications. These monoclonal antibodies, designed to enhance immune responses, have revealed a spectrum of immune-related adverse events (irAEs). While many irAEs exhibit favorable responses to corticosteroid or immunosuppressive therapy, most ICI-related endocrinopathies necessitate lifelong replacement therapy and pose significant clinical challenges. Adrenal insufficiency (AI), a noteworthy endocrine irAE, can manifest as primary AI (PAI) or secondary AI (SAI), resulting from adrenal or pituitary gland dysfunction, respectively. ICI-induced AI, albeit relatively infrequent, occurs in 1%–2% of patients receiving single-agent anti-Programmed Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) or Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) therapies and in a higher range of 4%–9% when ICIs are used in combinations. Recognizing and addressing ICI-induced PAI is crucial, as it often presents with acute and potentially life-threatening symptoms, especially considering the expanding use of ICI therapy. This review provides an updated overview of ICI-induced PAI, exploring its clinical, diagnostic, and radiological aspects.

Purpose: Opioid-induced constipation (OIC) is a common adverse effect of opioid therapy. We aim to identify the main barriers hindering clinical recommendations implementation and propose consensus solutions to improve OIC control in cancer patients.

Methods: Following collaborative and prioritization techniques, a scientific committee generated statements addressing possible barriers to optimal OIC management (related to patients, health providers and health care system), and potential interventions to overcome these barriers. An expert panel of 36 oncologists assessed the statements to reach a consensus.

Results: The survey consisted of 70 statements. Consensus was reached on 12/45 items related to barriers (26.6%) and on 19/25 items about corrective interventions (76%). The panel considered that patients are unaware of the existence of a specific OIC treatment, and their information sources are highly variable and unreliable. Regarding health providers, the panel considered that the oncologists prioritize symptoms such as diarrhea, pain, anxiety, or other treatment toxicities, over constipation. Work overload and bureaucratic requirements were the main barriers related to health care system. Regarding potential interventions, best-rated proposals included specific training programs development for primary care physicians and nurses, and multiplatform informative resources development for patients and caregivers, including precisely written instructions about OIC recognition and management. Oncologists assessed positively measures aiming to improve coordination between primary care physicians and oncologists, and nursing consultations implementation. The panel considered useful the OIC treatment algorithms simplification.

Conclusions: The expert panel identified the main barriers to optimal OIC management and suggested some feasible approaches to overcome these barriers.

Introduction

Squamous cell carcinoma of the anus (SCCA) is a rare tumor. While most patients with locally advanced disease are cured with chemo-radiotherapy, about a quarter eventually experience metastatic recurrence. Standard treatment for advanced disease is chemotherapy, but recently evidence on the activity of immunotherapy has been reported. We performed a systematic review and meta-analysis of prospective trials testing immune-checkpoint inhibitors (ICIs) in patients with SCCA.

Objective

We aimed to evaluate the overall response rate (ORR) and the disease control rate (DCR) of ICIs in patients with advanced SCCA.

Methods

We systematically searched PubMed, Embase, and Scopus, through December 31, 2022, for prospective trials assessing ICIs in patients with advanced SCCA. The primary and secondary endpoints were respectively ORR and DCR.

Results

Six prospective trials were included in the analysis, one of which was randomized. Overall, seven treatment arms and 347 patients have been analyzed. Five treatment arms tested ICIs as monotherapy and two arms examined ICIs in combination with cetuximab and bevacizumab, respectively. The pooled ORR was 13% (95%CI, 10%–17%), with a DCR of 57% (95%CI, 40%–74%). Results did not change in a sensitivity analysis, which excluded the two treatment arms testing the combination of ICIs with other drugs.

Conclusions

The efficacy of ICIs in SCCAs is low. Combination strategies with targeted drugs or chemotherapy might represent a better therapeutic strategy for these patients. Further studies are awaited to identify resistance mechanisms to ICIs and optimize their efficacy.