Safety and Efficacy of First-Line Pembrolizumab in Black Patients with Metastatic Non-Small Cell Lung Cancer.

INTRODUCTION: Pembrolizumab, an immune checkpoint inhibitor (ICI), has become an integral part of front-line treatment of metastatic non-small cell lung cancer (NSCLC). However, pivotal trials had significant underrepresentation of Black patients (pts). Lack of sufficient evidence regarding safety and efficacy of ICIs among minority racial groups poses a challenge in delivery of optimal cancer directed care. METHODS: We retrospectively reviewed pts with stage IV NSCLC treated with first-line pembrolizumab across three MedStar facilities between January 1, 2014, and May 3, 2019. Progression-free survival (PFS) and overall survival (OS) were primary endpoints and were calculated using the Kaplan-Meier method. Immune-related adverse events (irAEs) were assessed according to Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0). RESULTS: In total, 136 pts were identified, with 74 (54.4%) White, 53 (39%) Black, 2 (1.5%) Asian, and 7 (5.1%) other racial groups. Median age was 70 years in White pts and 65 years in Black pts (p < .01). There was no difference in median PFS (5.7 vs. 5.9 months; p = .651) or OS (11.8 vs. 12.4 months; p = .949) between White and Black pts. In the subset of patients whose tumors had high programmed death-ligand 1 (PD-L1) expression (≥50%), there was still no difference in efficacy by race. Median PFS (8.7 vs. 3.9 months; p = .843) and OS (14.7 vs. 11.3 months; p = .581) in White versus Black pts were not different. Incidence of irAEs in White versus Black pts was 24.3% and 22.6%, respectively (p = .83). CONCLUSION: We found no major differences in either safety or efficacy of first-line pembrolizumab between White and Black pts. Use of first-line pembrolizumab-based treatment in Black pts with stage IV NSCLC is safe and efficacious, based on these real-world data. IMPLICATIONS FOR PRACTICE: Immunotherapy has revolutionized treatment of solid and hematological malignancies. There are certain populations of patients underrepresented in the original trials including minority racial groups, patients with autoimmune diseases, and those with chronic viral illnesses. Our study focuses on Black patients with metastatic lung cancer who received pembrolizumab and concludes similar safety and response to treatment when compared with White patients. Black patients are an important demographic group in clinical practice often facing systemic health care disparities. This study paves a path for future studies in underrepresented populations receiving immunotherapy across various malignancies.

Combined Inhibition of EGFR and VEGF Pathways in Patients with EGFR-Mutated Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways could potentiate improved outcomes in patients with metastatic EGFR-mutated non-small cell lung cancer (NSCLC). The purpose of this systematic review and meta-analysis was to compare the efficacy of an EGFR tyrosine kinase inhibitor (TKI) plus a VEGF inhibitor with EGFR TKI alone for the treatment of EGFR-mutated NSCLC. RECENT FINDINGS: We systematically searched for randomized controlled trials (RCT) that involved patients with EGFR-mutated metastatic NSCLC treated with combination therapy versus EGFR TKI alone. In a pooled analysis of 5 studies, treatment with the combination therapy was associated with statistically significant improvements in progression-free survival (hazard ratio [HR] 0.63, 95% CI [0.54, 0.75]) when compared with control. However, pooled data from 4 studies revealed no statistically significant differences between the 2 groups for overall survival (HR 1.00, 95% CI [0.68, 1.52]) and the objective response rate (relative risk [RR] 1.05, 95% CI [0.97, 1.14]). In patients with metastatic EGFR-mutated NSCLC, treatment with EGFR TKI plus VEGF inhibition provided significant improvements in progression-free survival, but not in overall survival or objective response rate, when compared with treatment with EGFR TKI alone.

Role of Anti-EGFR Targeted Therapies in Stage III Locally Advanced Non-small Cell Lung Cancer: Give or Not to Give?

PURPOSE OF REVIEW: Identification of targetable mutations such as EGFR has allowed opportunity for Tyrosine Kinase Inhibitor (TKI) therapy for lung cancer treatment. EGFR-TKIs have revolutionized treatment of advanced EGFR mutant Non-Small Cell Lung Cancer (NSCLC), but there is little evidence that EGFR-TKI treatment is effective in stage III NSCLC. Here we discuss recent evidence supporting the use of EGFR-TKI therapy in combination with chemotherapy and radiation in stage III NSCLC. RECENT FINDINGS: Recent results of small trials testing EGFR-TKI therapy in combination with chemoradiation showed promising efficacy, improved outcomes, and a tolerable toxicity profile when administered to patients with EGFR mutant stage III NSCLC. However, strong supporting evidence regarding EGFR-TKI therapy in stage III NSCLC is lacking because previous trials involved a small patient population or were terminated due to slow participant accrual. Despite the lack of large randomized clinical trials, results from early-stage trials highlight promising future directions for investigating the use of EGFR-TKI therapy in stage III NSCLC treatment.

Redifferentiation of Differentiated Thyroid Cancer: Clinical Insights from a Narrative Review of Literature.

Background: Patients who have metastatic differentiated thyroid cancer (mDTC) frequently have negative diagnostic and/or post-therapy radioiodine scans. As a result, 131I therapy is frequently no longer considered a therapeutic option for these patients. However, with the knowledge of genomic alterations of patients with mDTC, the use of selected agents in specific patient groups may be used with the intention to re-establish 131I uptake (i.e., redifferentiation) and additional 131I therapy. The objectives of this narrative review are to present definitions of related terminology, a brief overview of the molecular mechanisms of redifferentiating agents, and a narrative review of the literature for redifferentiation in patients who have radioiodine refractory mDTC. Summary: We searched multiple electronic databases and reviewed the relevant English-language literature reported after 2010. Fourteen articles were included in this narrative review. Conclusions: Preliminary data suggest that select agents may offer potential for re-establishing 131I uptake in selected patients with radioiodine refractory mDTC (e.g., negative diagnostic and/or post-therapy radioiodine scans). These agents may also enhance uptake (e.g., uptake enhancement) in patients who have 131I uptake in mDTC on a diagnostic and/or post-therapy radioiodine scan. As a result, this may facilitate higher absorbed dose delivered (Gy (rad]) per 131I activity administered [GBq (mCi)]. This in turn may increase the likelihood of a better therapeutic effect for the planned administered 131I activity or a reduction in the originally planned administered 131I activity, while achieving the same intended therapeutic effect with potentially less untoward effects. Further studies are warranted to confirm these preliminary observations and to confirm acceptable subsequent 131I therapy responses after redifferentiation and/or uptake enhancement.

Integrating Tobacco Use Assessment and Treatment in the Oncology Setting: Quality Improvement Results from the Georgetown Lombardi Smoking Treatment and Recovery Program.

As part of the NCI's Cancer Center Cessation (C3i) initiative, we initiated, expanded, and maintained an evidence-based tobacco treatment program at the Georgetown Lombardi Comprehensive Cancer Center. We present a quality improvement (QI) assessment of the implementation process and patient-level outcomes. At two hematology/oncology outpatient clinical sites, five oncology-based teams (clinical administrators, clinical staff, pharmacy, information technology, and tobacco treatment staff) developed implementation strategies for opt-out patient assessment and enrollment, centralized tobacco treatment, audit, feedback, and staff training. Among eligible patients (tobacco use in ≤30 days), we assessed demographic, clinical, and tobacco-related characteristics to examine predictors of enrollment (baseline completed), treatment engagement (≥one sessions completed), and self-reported 7-day abstinence (6 months post-enrollment). Across both sites, medical assistants screened 19,344 (82.4%) patients for tobacco use, which identified 1345 (7.0%) current tobacco users, in addition to 213 clinician referrals. Of the 687/1256 (54.7%) eligible patients reached, 301 (43.8%) enrolled, and 199 (29.0%) engaged in treatment, of whom 74.5% were African American and 68% were female. At the larger site, significant multivariate predictors of enrollment included African American race (vs. white/other) and clinician referral (vs. MA assessment). Treatment engagement was predicted by greater nicotine dependence, and abstinence (27.4%) was predicted by greater treatment engagement. In summary, the systematic utilization of multiple oncology-based teams and implementation strategies resulted in the development and maintenance of a high-quality, population-based approach to tobacco treatment. Importantly, these strategies addressed inequities in tobacco treatment, as the program reached and engaged a majority-African-American patient population. Finally, the opt-out patient assessment strategy has been implemented in multiple oncology settings at MedStar Health through the Commission on Cancer's Just Ask program.

Impact of Baseline Clinical Biomarkers on Treatment Outcomes in Patients With Advanced NSCLC Receiving First-line Pembrolizumab-Based Therapy.

BACKGROUND: While the introduction of immune checkpoint inhibitors (ICI) such as pembrolizumab has significantly improved survival for patients with metastatic non-small cell lung cancer (NSCLC), there remains a need for improved predictive and prognostic biomarkers. PATIENTS AND METHODS: We conducted a retrospective, 3-center study using electronic medical record data for patients with stage IV NSCLC treated with first-line pembrolizumab, either as monotherapy or in combination with chemotherapy, between 2014 and 2019. We categorized variables as covariates or confounders. Covariates, which were the focus of analysis due to their emerging prognostic value, included pretreatment body mass index (BMI), neutrophil-to-lymphocyte ratio (NLR), albumin, and antibiotic exposure. Confounders, which highlighted characteristics for each patient and their cancer, included sex, age at start of immunotherapy, Programmed death-ligand 1 (PD-L1) expression, performance status (PS), tumor mutational burden and whether pembrolizumab was given as monotherapy or in combination with chemotherapy. The association between these variables with time to treatment failure (TTF) and overall survival (OS) was assessed using Kaplan-Meier method and Cox proportional hazards models. RESULTS: One hundred thirty-six patients were included in our study. Antibiotics usage, serum albumin, and NLR have univariate relationships with TTF. Serum albumin, NLR, and BMI were associated with OS in univariate analyses. In our multivariate analysis, antibiotic usage had a strong negative association with TTF when adjusting for all 6 confounders. CONCLUSION: Pretreatment usage of antibiotics, as well as albumin, NLR, and BMI have potential to predict treatment outcomes in patients with advanced NSCLC receiving first-line immunotherapy.

Racial disparities in immune-related adverse events of immune checkpoint inhibitors and association with survival based on clinical and biochemical responses.

BACKGROUND: Immune checkpoint inhibitors (ICPi) cause various immune-related adverse events (irAE) with thyroid dysfunction as a commonly reported abnormality. There is increasing evidence showing positive association with development of irAE and survival. However, prior trials with ICPi had underrepresentation of minorities with < 5% African Americans. AIM: To evaluate the association between development of irAE and survival outcomes among a racially diverse patient population. METHODS: Data on patients with stage IV solid malignancies treated with programmed cell death-protein 1/programmed death ligand 1 blockers between January 2013 and December 2018 across MedStar Georgetown Cancer Institute facilities were retrospectively reviewed. Patients treated with cytotoxic T-lymphocyte-associated protein 4 inhibitors were excluded. Progression free survival (PFS) and overall survival (OS) were primary endpoints and were calculated using Kaplan-Meier methods and Wilcoxon rank sum test for comparison. RESULTS: Out of 293 patients who met eligibility criteria, 91 pts (31%) had any grade irAE; most common AE were endocrine (40.7%) specifically TSH elevation, dermatological (23.1%) and rheumatologic (18.7%). Proportion of irAE was significantly higher in Caucasians vs African Americans (60.4% vs 30.8%), in patients with low programmed death ligand 1, lower LDH, older age, and those who had more treatment cycles with ICPi. Rate of progression was lower in patients with irAE (30.8% vs 46.0%, P = 0.0140). Median PFS (5.8 vs 3.0 mo, P = 0.0204) and OS (17.1 vs 7.2 mo, P < 0.0001) were higher with irAE. Statistically significant difference in OS (17.1 vs 8.6 mo, P = 0.0002) but not in PFS (5.8 vs 3.3 mo, P = 0.0545) was noted with endocrine irAE. No differences in survival were observed among other commonly reported irAE. Differences in survival among subgroups of patients with irAE are described. CONCLUSION: Development of irAE positively correlated with improved PFS and OS as reported in previous studies. To our knowledge, this is the first study observing differences in OS favoring endocrine AE and Caucasian race. These factors may be potential surrogate markers of prognosis pending replication of these results in large-scale studies.

Metastasis of laryngeal squamous cell carcinoma to bilateral thigh muscles.

Importance. Laryngeal cancer infrequently results in distant metastases, but metastasis to skeletal muscle is extremely uncommon. Observations. A 55-year-old male presenting with progressive dyspnea and hoarseness was found to have Stage IVA T4aN2cM0 laryngeal cancer and eventually underwent total laryngectomy. Before the patient could be started on adjuvant chemoradiation, the patient developed masses on both thighs. Biopsy revealed metastatic squamous cell carcinoma consistent with the primary laryngeal cancer. He was offered palliative chemotherapy; however, he developed new soft tissue masses to the left of his stoma and in the prevertebral area one week later. He also had new cervical and supraclavicular nodes and a pathological compression fracture of L3. Patient died within 4 months of diagnosis. Conclusions. Distant metastasis such as skeletal metastasis portends a poor prognosis. Further studies are required to determine the best course of treatment in these patients.

Bevacizumab and Angiogenesis Inhibitors in the Treatment of CNS metastases: the Road less Travelled.

The incidence of central nervous system (CNS) metastases secondary to solid tumors is increasing. As more effective systemic therapy is being used in patients with solid tumors, patients with cancer live longer and are ultimately at higher risk for CNS metastases. However, CNS metastases remain challenging to treat because of limited available therapeutic options. This article reviews mechanisms of CNS metastases, the use of bevacizumab and other angiogenesis inhibitors in the treatment of recurrent and front-line CNS metastases, as well as emerging issues of resistance to anti-angiogenic therapy.

Management of endocrine manifestations and the use of mitotane as a chemotherapeutic agent for adrenocortical carcinoma.

Adrenal cortical carcinoma (ACC) is a rare malignancy in which patients have poor overall 5-year survival. Patients with ACC can present with symptoms of hormone excess, including Cushing's syndrome, virilization, feminization, or--less frequently--hypertension with hypokalemia. In many patients with ACC, advanced disease at presentation precludes surgery or is followed by local relapse or distant metastatic disease that cannot be managed surgically. In these instances, chemotherapy is often tried, but its limited efficacy all too often leaves the problem of persistent hormonal excess. Physicians who treat patients with ACC and severe hypercortisolism should recognize that uncontrolled hormone production is a malignant disease, which has severe consequences that require aggressive management. Because chemotherapy benefits only a small percentage of patients, steroidogenesis inhibitors, including mitotane, ketoconazole, metyrapone, and etomidate, should be used singly or in combination even as chemotherapy is administered. Diligent management with frequent adjustments is required, especially in patients with chemotherapy-refractory tumors that continue to grow. In the absence of randomized, controlled trials, adjuvant use of mitotane remains controversial, although the authors of a recent case-control study argue for its use. Despite difficulty administering effective doses, most clinicians agree that mitotane should be used if the tumor cannot be removed surgically or should be used as adjuvant therapy if there is a high likelihood of recurrence. The option of long-term monotherapy is restricted to patients who tolerate mitotane and either experience a clinical response or are at high risk for recurrence. Recommendations are provided to help manage patients with this difficult disease and to improve the quality of their lives.