Cyclin-Dependent Kinase 4/6 Inhibitors and Dermatologic Adverse Events: Results from the EADV Task Force "Dermatology for Cancer Patients"

Treatment with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), has demonstrated significantly improved progression-free survival in patients with hormone receptor-positive, HER2-negative, advanced breast cancer, when used in combination with endocrine therapies. However, limited data exists on its cutaneous adverse events (AE). The aim of our retrospective study was to investigate the prevalence, types and management of cutaneous AE during CDK4/6i. 79 adult advanced breast cancer patients affected by 125 skin adverse events during treatment with CDK4/6i were recruited at eleven centers. The most frequent cutaneous reactions were pruritus (49/79 patients), alopecia (25/79), and ec-zematous lesions (24/79). We showed that skin reactions are usually mild in severity, and prompt management may limit the negative impact on patients, facilitating beneficial continuation of oncologic treatment

Treating patients with ALK-rearranged non-small-cell lung cancer: mechanisms of resistance and strategies to overcome it

Anaplastic lymphoma kinase (ALK) rearrangement is detected in 3-7% of patients with non-small-cell lung cancer. Crizotinib is an ALK inhibitor, which was approved in 2011 for the treatment of ALK-positive lung cancer. Despite the initial enthusiasm, most of the patients develop resistance within the first year of treatment. The main mechanisms are secondary mutations and bypass track activation. Moreover, crizotinib has low penetration into the central nervous system. The need to overcome these limitations has led to the development of second-generation inhibitors that have better effectiveness against crizotinib-resistant mutations and brain metastases. Ceritinib and alectinib are the only approved drugs of this group. Many ongoing trials try to define the most appropriate agent for the treatment of ALK-positive lung cancer depending on the responsible mechanism. This review focuses on the current data regarding the potential mechanisms of resistance to ALK inhibitors and the strategies to overcome it

Lung Metastasis from Fibrosarcomatous Dermatofibrosarcoma Protuberans of the Vulva: A Rare Case Report

Identification of t(17;22) translocation remains pivotal for the management of metastatic fibrosarcomatous dermatofibrosarcoma protuberans of the vulva. © Lippincott Williams & Wilkins

Targeted therapy for oesophageal cancer: an overview

Oesophageal cancer (OC), is an aggressive cancer constituting a major cause of cancer-related deaths worldwide. Recent advances in surgical techniques, incorporation of new therapeutic approaches-adjuvant/neoadjuvant chemoradiotherapy-and integration of new cytotoxic drugs into the management of oesophageal cancer have increased the response rate percentages to 40-50%, with minor impact on the overall survival. The need for an efficacious therapy with minimal toxicity along with a better understanding of molecular pathways of oesophageal carcinogenesis has led to the development of novel anticancer agents. These agents have targeted mechanisms of action such as: (1) inhibitors of the ErbB receptor family, (2) vascular endothelial growth factor (VEGF) inhibitors, (3) selective inhibitors of cycloxygenase-2, (4) matrix metalloproteinase inhibitors, (5) cell-cycle regulators, and (6) promoters of apoptosis. The incorporation of these agents into combined modality treatment schedules for advanced and early stage tumors together with the identification of patients who will most likely benefit will provide novel opportunities in the treatment of oesophageal cancer

Immune Checkpoint Inhibitor-Related Pneumonitis

Immune checkpoint inhibitors are novel agents that have been proved efficacious in a variety of cancer types, but they are associated with a unique set of organ-specific, immune-related adverse events. Among them, immune-related pneumonitis requires special attention because it is difficult to diagnose and potentially lethal. Accumulating real-world epidemiological data suggest that immune-related pneumonitis is more frequent than previously reported. Its diagnosis requires exclusion of other causes and assessment of radiographic features on high-resolution CT of the chest. Management of immune-related pneumonitis is based on the use of immunosuppressants. Future research should be focused on finding predictive biomarkers for immune-related pneumonitis as well as optimizing its management. © 2020 S. Karger AG, Basel. Copyright: All rights reserved

Cyclin-dependent kinase (CDK) inhibitors in solid tumors: a review of clinical trials

Cyclin-dependent kinases (CDKs) play a key regulating role in the cell cycle, which is almost universally altered in cancer, leading to sustained proliferation. Early pan-CDK inhibitors showed poor results in clinical trials for solid malignancies, as the lack of selectivity produced significant toxicity. The production of more selective inhibitors led to significant developments in cancer therapy, as CDK4/6 inhibitors in combination with endocrine therapy changed the landscape of the treatment of hormone-receptor positive (HR +) metastatic breast cancer. Recently, Trilaciclib demonstrated benefits regarding hematological toxicity compared to placebo when administered in combination with chemotherapy in small cell lung cancer. Newer agents, such as SY-5609, a selective CDK7 inhibitor, have also shown promising results in early clinical trials. In this paper, we review the data from clinical trials of CDK inhibitors in solid tumors, either as a monotherapy or in combination with other agents, with an emphasis on novel agents and potential new indications for this drug class

Significant Increase in Blood Pressure Following BNT162b2 mRNA COVID-19 Vaccination among Healthcare Workers: A Rare Event

This brief report examined the frequency and characteristics of a significant blood-pressure (BP) increase after Pfizer-BioNTech BNT162b2 vaccination among healthcare workers who were advised to measure their BP at home. A total of 797 participants (mean age 48.1 ± 10.8 years, 63% women, 39% smokers) were included in the analysis. Seven participants reported an increase in their BP (three in the range of grade 2 and four in the range of grade 3 hypertension). Only one participant had a history of treated hypertension. The BP increase was observed at the end of the first week after the first dose, lasted for 3 to 4 days, and recurred promptly after the second dose. Only one case required hospitalization, mainly due to a history of cardiovascular disease (follow-up). Individuals experiencing a BP increase compared with those not reporting issues with their BP had a higher mean age and similar distribution of sex and non-smoking status. In conclusion, a significant BP increase after Pfizer-BioNTech vaccination seems to be rare and of a benign and transient nature. Monitoring the BP before and after vaccination might be advisable only for selected individuals with a high cardiovascular risk. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Mechanisms of resistance to cyclin-dependent kinase 4/6 inhibitors

Cyclin-dependent kinase (CDK) 4/6 inhibitors have emerged in the treatment of metastatic hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. However, most patients will eventually present disease progression, highlighting the inevitable resistance of cancer cells to CDK4/6 inhibition. Several studies have suggested that resistance mechanisms involve aberrations of the molecules that regulate the cell cycle, and the re-wiring of the cell to escape CDK4/6 dependence and turn to alternative pathways. Loss of retinoblastoma function, overexpression of CDK 6, upregulation of cyclin E, overexpression of CDK 7, and dysregulation of several signaling pathways, notably the PI3/AKT/mTOR pathway, have been implicated in the development of resistance to CDK4/6 inhibitors. Overlap with endocrine resistance mechanisms might be possible. Combinational therapeutic strategies should be explored in order to prevent resistance and optimize the management of patients after progression under CDK 4/6 inhibition. © 2021, The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature