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.

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.

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.

A Systematic Review and Meta-Analysis of Clinical Characteristics and Outcomes in Patients With Lung Cancer with Coronavirus Disease 2019.

Cancer is considered to be an independent risk factor for severe illness and higher mortality in patients with coronavirus disease 2019 (COVID-19). These adverse outcomes have been suspected to be more severe in patients with lung cancer. The objective of this systematic review and meta-analysis is to outline patient characteristics, challenges in diagnosis and treatment, and outcomes of patients with lung cancer with COVID-19. A comprehensive search was conducted using EMBASE and PubMed databases using the terms "COVID" and "cancer." Studies that reported clinical characteristics or outcomes of patients with lung cancer with COVID-19 were then systematically identified. Meta-analysis for COVID-19 related mortality associated with lung cancer compared with other cancer types was conducted. The results were reported as OR and confidence intervals using the mixed-effects logistic regression model. The most frequently reported clinical findings in patients with lung cancer with COVID-19 were fever and cough, with 68% and 61%, respectively. Laboratory and radiographic findings were consistent with broadly reported data. The meta-analysis noted a statistically significant increase in mortality rate in patients with lung cancer compared with other patients with cancer, with an OR of 1.62 (95% confidence interval: 1.06-2.48). Patients with lung cancer with COVID-19 also reflected greater severity of illness and higher rates of intensive care unit admissions and mechanical ventilation. COVID-19 in patients with lung cancer is associated with severe disease and increased mortality relative to patients with other malignancies and the general population. There is conflicting evidence on the effect of specific lung cancer treatments on outcomes. Until more definitive data is available, lung cancer-directed treatment should be continued or restarted as early as possible in mild to moderate cases to prevent worsening and cancer-related mortality.

Rare case of hepatocellular carcinoma metastasising to the pituitary and cavernous sinus causing panhypopituitarism and bilateral ophthalmoplegia.

Pituitary metastases, especially from a primary hepatocellular carcinoma (HCC), are rare. Review of the literature revealed only few cases reporting pituitary metastases complicated by panhypopituitarism from HCC. Calvarial metastases from HCC are even more rare. Here, we present a unique case of primary HCC with metastases to both the calvarium and the pituitary causing panhypopituitarism and bilateral ophthalmoplegia, respectively. To our knowledge, this is the first reported case of two unique and rare complications from metastatic HCC.

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.