Management of toxicities associated with immune checkpoint inhibitors.

Immune-related adverse events (irAEs) encompass a diverse range of toxicities following treatment with immune checkpoint inhibitors (ICIs), each with distinctive symptoms, severities, and outcomes. irAEs can affect any organ and are potentially fatal, so early diagnosis is key in preventing serious events. irAEs can be fulminant, requiring immediate attention and intervention. Management of irAEs involves the use of systemic corticosteroids and immunosuppressive agents in addition to any disease-specific therapeutics. Making the decision to rechallenge with ICIs is not always clear and involves weighing the risks and clinical benefits of continuing ICI therapy. Here, we review the consensus recommendations on managing irAEs and discuss current challenges in clinical care caused by these toxicities.

Emerging New Targets in Systemic Therapy for Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a heterogeneous cancer composed of distinct molecular and pathologic subtypes. Unfortunately, MPM is aggressive, and current therapies for advanced, unresectable disease remain limited to cytotoxic chemotherapy and immunotherapy. Our understanding of the genomic landscape of MPM is steadily growing, while the discovery of effective targeted therapies in MPM has advanced more slowly than in other solid tumors. Given the prevalence of alterations in tumor suppressor genes in MPM, it has been challenging to identify actionable targets. However, efforts to characterize the genetic signatures in MPM over the last decade have led to a range of novel targeted therapeutics entering early-phase clinical trials. In this review, we discuss the advancements made thus far in targeted systemic therapies in MPM and the future direction of targeted strategies in patients with advanced MPM.

An Era of Advances in Systemic Therapies for Advanced Thyroid Cancer.

Thyroid carcinomas comprise distinct pathologic subtypes. However, advancements in characterizing the molecular tumorigenesis of thyroid cancers have changed the treatment paradigm in the past decade. Genetic profiling has become an integral component of personalizing cancer care. Oral kinase inhibitors are currently standard-of-care therapies for progressive, radioactive iodine (RAI)-refractory differentiated thyroid carcinomas (DTCs) and medullary thyroid carcinomas (MTCs). Sorafenib, lenvatinib, and cabozantinib are multikinase inhibitors approved for patients with metastatic RAI-refractory DTC, whereas vandetanib and cabozantinib are approved for patients with MTC. Management of thyroid carcinomas has evolved such that targeted therapies have become therapeutic options for patients with BRAF, RET, NTRK, ALK, and ROS1 alterations and even have reported efficacy in anaplastic thyroid carcinomas. In this article, we review the advances made over the years in the treatment of metastatic thyroid carcinoma and focus on the systemic therapies that have recently transformed the treatment landscape of advanced disease.

Repotrectinib in a Patient With NTRK Fusion-Positive Pancreatic Carcinoma and Congenital Long QT Syndrome.

Repotrectinib in a patient with NTRK fusion-positive pancreatic carcinoma and congenital long QT syndrome.

Metastatic HER2-amplified non-small-cell lung cancer treated with trastuzumab deruxtecan.

Human epidermal growth factor receptor 2 (HER2) alterations can occur as gene mutations, gene amplification or protein overexpression. DESTINY-Lung01 and DESTINY-Lung02 demonstrated the efficacy of trastuzumab deruxtecan in the subsequent line setting in patients with unresectable or metastatic HER2-mutated non-small-cell lung cancer (NSCLC). Trastuzumab deruxtecan has not been studied in select patients with HER2-amplified NSCLC. Here, we present the first reported case of metastatic HER2-amplified NSCLC treated with trastuzumab deruxtecan with a durable response to therapy.

Update on Lorlatinib: Role in Reducing the Risk of Disease Progression in ALK-Positive NSCLC.

Lorlatinib is an oral third-generation inhibitor of anaplastic lymphoma kinase (ALK) with activity in advanced ALK-positive non-small cell lung cancer (NSCLC) in both the first and subsequent line setting. Superior systemic and intracranial efficacy of lorlatinib over crizotinib, a first-generation ALK tyrosine kinase inhibitor (TKI), in treatment-naïve patients with advanced ALK-positive NSCLC was demonstrated by the phase 3 CROWN trial. Lorlatinib retains anti-tumor effect against single and some compound ALK resistance mutations after disease progression on first- and second-generation ALK TKIs. Currently, alectinib, brigatinib, ceritinib, crizotinib and lorlatinib are approved for treatment of advanced ALK-positive NSCLC. However, no head-to-head studies have directly compared lorlatinib to second-generation ALK inhibitors. Herein, we aim to provide an overview of the efficacy and safety of lorlatinib and discuss where lorlatinib stands in the therapeutic approach to advanced ALK-positive NSCLC.

Women in Emergency Medicine Residency Programs: An Analysis of Data From Accreditation Council for Graduate Medical Education-approved Residency Programs.

OBJECTIVE: Understanding the factors associated with attracting women to a residency program would help residency program leadership build programs that are appealing to women candidates. The objective of this study was to identify factors associated with the percentage of women residents in emergency medicine (EM) residency programs. METHODS: A list of 161 Accreditation Council for Graduate Medical Education-approved EM residencies was compiled. The public websites for each of the residencies was queried for information on the following variables: residency region (Midwest, Northeast, South, West), residency length (3 years vs. 4 years), sex of the department chair, sex of the program director (PD), percentage of women faculty, and the number of residents by graduation class and sex. RESULTS: The websites of 161 EM residencies were reviewed. Complete data were available from a total of 143 programs representing 4,547 residents from the studied classes of 2014, 2015, and 2016. Overall, 38% were women (n = 1,743). The percentage of women residents per program varied from 0% to 68% across residency programs. There was no association between the percentage of women residents and residency region, sex of the department chair, and sex of the PD. CONCLUSIONS: In this study, there was no evidence that EM residencies with a greater percentage of women faculty and women in select leadership roles had a greater percentage of women residents. There was also no evidence for regional variability in women's selection of residency programs. This study was limited to publicly available data and cannot address the many other complex factors which may play a role in women's decision making when choosing a residency.