Advances in Endocrine Therapy for Hormone Receptor-Positive Advanced Breast Cancer.

PURPOSE OF REVIEW: To provide an overview of the current management of hormone receptor-positive (HR +) advanced breast cancer as well as highlight ongoing clinical investigation and novel therapies in development. RECENT FINDINGS: CDK4/6 inhibition plus endocrine therapy is standard front-line therapy for HR + advanced breast cancer. Continuation of CDK4/6 inhibitors in combination with alternative endocrine therapy has been evaluated in the second-line setting. Alternatively, endocrine therapy in combination with PI3K/AKT pathway targeting agents has been studied, particularly in patients with PI3K pathway alterations. The oral SERD elacestrant has also been evaluated in patients with ESR1 mutation. Many novel endocrine agents and targeted agents are in development. An improved understanding of combination therapies and sequencing of therapies is needed to optimize the treatment paradigm. Biomarker development is needed to guide treatment decisions. Advances in the treatment of HR + breast cancer have resulted in improved patient outcomes in recent years. Continued development efforts with identification of biomarkers to better understand response and resistance to therapy are needed.

Extranodal diffuse large B-cell lymphoma presenting with extensive organ involvement.

Extranodal involvement in diffuse large B-cell lymphoma (DLBCL) is defined as disease outside of the lymph nodes and occurs in up to one-third of patients, though multiorgan extranodal involvement is rare. Here, we describe a case of a patient presenting with widely metastatic lesions, including involvement of the lung, parotid gland, breast, pancreas, femur and multiple soft tissue masses, with initial concern for primary breast malignancy. Breast pathology and imaging were consistent with triple-expressor, double-hit stage IV high-grade B-cell lymphoma with extensive extranodal involvement. Extranodal involvement is a poor prognostic factor associated with high rates of treatment failure, and novel therapies targeting CD19 are currently being studied for relapsed and refractory DLBCL. Extranodal disease is a complex entity that can involve virtually any organ system and should be considered for new presentations of malignancy.

ChemoPalRx-A Mobile App That Enhances Chemotherapy Prescription Accuracy: A Cross-Sectional Study.

PURPOSE: ChemoPalRx is a novel provider order entry mobile application for chemotherapy. This study aims to evaluate the accuracy of prescribing chemotherapy using ChemoPalRx versus handwritten orders at a safety-net hospital in Los Angeles. METHODS: In a cross-sectional study from October 2019 to December 2019, we evaluated all outpatient chemotherapy orders for accuracy. Our primary predictor was type of prescription, dichotomized as handwritten or ChemoPalRx. Primary outcome was accuracy, dichotomized as accurate if no error was made on an order and as inaccurate if any error was made. Preplanned subgroup analyses were performed with covariates including provider experience, complexity of order, and day of order submission. We characterized error type and analyzed our data using univariate and multivariate logistic regression models. RESULTS: Among 288 orders (78.5% handwritten; 21.5% ChemoPalRx), prescription accuracy was higher among ChemoPalRx (93.5%) compared with handwritten orders (81.4%; P = .012). In multivariate analysis, prescription accuracy remained superior for ChemoPalRx after adjusting for provider experience, complexity of order, and day of order submission (adjusted odds ratio, 1.82; P = .012). Compared with handwritten orders, ChemoPalRx orders had less missing or incorrect information (1.6% v 13.7%; P = .0016). ChemoPalRx orders were also more accurate on prescriptions that contained two or fewer medications (92.2% v 80.2%; P = .032), submitted on the highest patient-volume clinic day of the week (96.7% v 83.2%; P = .035), and generated by a senior fellow or an attending (97.3% v 76.9%; P = .001). CONCLUSION: ChemoPalRx is associated with improved chemotherapy prescription accuracy over handwritten orders in the safety-net hospital setting and may serve as an alternative prescribing tool for oncology practices.

Correlation of Physical Exam Findings with Fever in Patients with Skin and Soft Tissue Infections.

INTRODUCTION: The objectives of this study were to determine the prevalence of fever in adult ED patients with skin and soft tissue infections (SSTI) and to determine which, if any, physical exam, radiograph and laboratory test findings were associated with fever. METHODS: We conducted a prospective, observational study at an urban county trauma center of adults who presented to the ED for evaluation of suspected SSTI. ED providers measured area of erythema and induration using a tape measure, and completed data sheets indicating comorbid conditions and the presence or absence of physical exam findings. Fever was defined as any recorded temperature ≥ 38°C during the first six hours of ED evaluation. RESULTS: Of the 734 patients enrolled, 96 (13.1%) had fever. Physical and laboratory exam findings associated with the presence of a fever in multivariable logistic regression were the area of erythema, particularly the largest quartile of area of erythema, 144 - 5,000 cm2, (odd ratio [OR] = 2.9; 95% confidence interval [CI] [1.6 - 5.2]) and leukocytosis (OR = 4.4, 95% CI [2.7 - 7.0]). Bullae, necrosis, streaks, adenopathy, and bone involvement on imaging were not associated with fever. CONCLUSION: Fever is uncommon in patients presenting to the ED for evaluation of suspected SSTI. Area of erythema and leukocytosis were associated with fever and should be considered in future decision rules for the evaluation and treatment of SSTI.

A Multicenter, Open-Label Phase II Clinical Trial of Combined MEK plus EGFR Inhibition for Chemotherapy-Refractory Advanced Pancreatic Adenocarcinoma.

PURPOSE: On the basis of preclinical evidence of synergistic activity between MEK and EGFR inhibitors in pancreatic ductal adenocarcinoma (PDAC), we evaluated the safety and efficacy of selumetinib, a MEK1/2 inhibitor, plus erlotinib in patients with previously treated advanced PDAC. EXPERIMENTAL DESIGN: In this single-arm phase II trial, eligible patients received the combination of erlotinib 100 mg plus selumetinib 100 mg daily in 3-week cycles. Study assessments included measurement of clinical outcomes, with a primary endpoint of overall survival, and exploration of potential molecular predictors of treatment benefit. RESULTS: Forty-six patients were enrolled and received a median of two cycles (range, 1-7). Although no objective responses were observed, 19 patients (41%) showed evidence of stable disease for ≥6 weeks, and 13 of 34 patients (38%) had a CA19-9 decline ≥50%. Median progression-free survival was 1.9 months [95% confidence interval (CI), 1.4-3.3 months], with a median overall survival of 7.3 months (95% CI, 5.2-8.0 months). Common adverse events included rash, diarrhea, and nausea/vomiting. Patients with tumors exhibiting an epithelial phenotype (demonstrated by a high level of E-cadherin expression) were more likely to be sensitive to study treatment. Tumor-derived DNA was detectable in plasma from the majority of patients using next-generation digital DNA sequencing, and its relative abundance correlated with tumor burden. CONCLUSIONS: A therapeutic strategy of dual targeted inhibition of the MEK and EGFR pathways shows modest antitumor activity in pancreatic cancer. Specific molecular subtypes may derive greatest benefit from this combination. Further exploration, both with more potent MEK inhibitors and in molecularly enriched patient subsets, is warranted.