A Phase 2 Study of Docetaxel, Ramucirumab, and Pembrolizumab for Patients With Metastatic or Recurrent Non-Small-Cell Lung Cancer (NSCLC) who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade.

Background: There is an urgent and unmet need for more effective treatment options for patients with metastatic and recurrent non-small-cell lung cancer (NSCLC) who progressed on platinum-based therapy, immune checkpoint inhibitors (ICI), and targeted therapies. Currently, the combination of docetaxel (D) and ramucirumab (R) is the next best salvage therapy with a modest historical progression free survival (PFS) of 4.5 months and 6-month PFS rate of 37% predating the era of ICI use.

A Safety Analysis of Programmed Death 1 Pathway Inhibitors in Patients With Solid Tumor Malignancies and Preexisting Autoimmune Disease.

Objective: The aim of this study was to characterize the safety of programmed death 1 inhibitors in patients with preexisting autoimmune disease.

Methods: A medical records review study was conducted on adults with solid tumor malignancies who received ≥1 dose of pembrolizumab or nivolumab at Emory Healthcare from September 4, 2014 until December 31, 2019. All autoimmune patients were included (n = 77), whereas the nonautoimmune patients were randomized and the first 156 patients were included in a 2:1 ratio to autoimmune patients.

Durvalumab and tremelimumab with or without stereotactic body radiation therapy in relapsed small cell lung cancer: a randomized phase II study.

Background: Immune checkpoint blockade (ICB) targeting programmed cell death protein 1 and cytotoxic T lymphocyte-associated protein 4 has achieved modest clinical activity as salvage therapy in relapsed small cell lung cancer (SCLC). We conducted this signal-finding study to assess the efficacy of ICB with or without radiation in relapsed SCLC.

Methods: Patients with relapsed SCLC and ≤2 previous lines of therapy were randomized to (1) arm A: durvalumab (D) 1500 mg/tremelimumab (T) 75 mg (intravenously every 4 weeks without stereotactic body radiation therapy (SBRT)) or (2) arm B: immune-sensitizing SBRT to one selected tumor site (9 Gy × 3 fractions) followed by D/T.

Phase Ib Study of Crizotinib plus Pembrolizumab in Patients with Previously Untreated Advanced Non-Small Cell Lung Cancer with ALK Translocation.

Lessons Learned: This study evaluating first-line crizotinib plus pembrolizumab in patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) was terminated early because increased availability of second-generation ALK inhibitors resulted in difficulty identifying and accruing eligible patients. In the small number of patients enrolled, elevated transaminases were the most common treatment-related toxicity. No other relevant toxicities were observed.

Trimodality Therapy in the Treatment of Stage III N2-Positive Non-Small Cell Lung Cancer: A National Cancer Database Analysis.

Background: Significant controversy remains regarding the care of patients with clinical stage III (N2-positive) NSCLC. Although multimodality therapy is effective, the roles of surgery, chemotherapy, and radiotherapy are not fully defined and the optimal treatment approach is not firmly established. We analyzed outcomes and predictors associated with trimodality therapy (TT) in the National Cancer Database.

Survival Outcomes With Thoracic Radiotherapy in Extensive-Stage Small-Cell Lung Cancer: A Propensity Score-Matched Analysis of the National Cancer Database.

Background: The prognosis of patients with extensive-stage small-cell lung carcinoma (ES-SCLC) is poor. The benefit of consolidative thoracic radiation therapy (TRT) in ES-SCLC has been inconclusive, and its use inconsistent. The objective of this study was to evaluate overall survival (OS) of ES-SCLC patients treated with chemotherapy (CT) with or without TRT using an administrative database approach.

Concurrent chemoradiotherapy with weekly versus triweekly cisplatin in locally advanced squamous cell carcinoma of the head and neck: Comparative analysis.

Background: Cisplatin-based chemoradiotherapy is standard of care for locally advanced squamous cell carcinoma of the head and neck. This systemic review compared efficacy and safety of weekly vs triweekly cisplatin in locally advanced squamous cell carcinoma of the head and neck.

Methods: Among 1500 prospective studies published from 1970 to 2015, 39 (18 weekly, 21 triweekly) including 3668 patients qualified for inclusion.

Personalized therapy for lung cancer: striking a moving target.

Molecular targeted therapy heralded a new era for the treatment of patients with oncogene-driven advanced-stage non-small-cell lung cancer (NSCLC). Molecular testing at the time of diagnosis guides therapy selection, and targeted therapies in patients with activating mutations in EGFR, BRAF, and rearrangements in anaplastic lymphoma kinase (ALK) and ROS1 have become part of routine care. These therapies have extended the median survival from a mere few months to greater than 3 years for patients with stage 4 disease.

Immune checkpoint inhibitors in small cell lung cancer.

Small cell lung cancer (SCLC) is a rapidly progressive cancer that often debilitates patients within months of detection and quickly becomes refractory to the limited options of therapy. While SCLC is not generally considered an immunogenic tumor, clinical experience suggests that patients with robust immune response manifesting as paraneoplastic syndrome are more likely to present with limited stage of the disease and tend to have a better prognosis. Monoclonal antibodies targeting critical negative regulators of immune response, so called immune checkpoints, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) have expanded the application of immune-based therapies to increasing number of advanced stage cancers.

Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: A systematic analysis of the literature.

Background: Monoclonal antibodies against programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) are effective therapies in patients with non-small cell lung cancer (NSCLC). Herein, the authors performed a systematic review investigating differences in the toxicities of PD-1 and PD-L1 inhibitors.

Methods: An electronic literature search was performed of public databases (MEDLINE, Excerpta Medica dataBASE [EMBASE], and Cochrane) and conference proceedings for trials using PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, and avelumab) in patients with NSCLC.

Concomitant Chemotherapy and Radiotherapy with SBRT Boost for Unresectable Stage III Non-Small Cell Lung Cancer: A Phase I Study.

Objectives: Stereotactic body radiation therapy (SBRT) is now the standard of care in medically inoperable stage I NSCLC, yielding high rates of local control. It is unknown whether SBRT can be safely utilized in the locally advanced NSCLC setting. This multi-institution phase I study evaluated the safety of 44 Gy of conventionally fractionated thoracic radiation with concurrent chemotherapy plus dose-escalated SBRT boost to both the primary tumor and involved mediastinal lymph nodes.

Pulmonary Sarcomatoid Carcinoma: An Analysis of the National Cancer Data Base.

Introduction: Pulmonary sarcomatoid carcinoma (PSC) is a grouping of 5 rare non-small-cell lung cancer (NSCLC) subtypes. We studied the clinical characteristics and outcomes of PSC utilizing the National Cancer Data Base (NCDB), an oncology outcomes database.

Methods: The NCDB lung cancer database was queried from 1998 to 2011 for PSC using ICD-O-3 codes.

Comparison of Concurrent Use of Thoracic Radiation With Either Carboplatin-Paclitaxel or Cisplatin-Etoposide for Patients With Stage III Non-Small-Cell Lung Cancer: A Systematic Review.

Importance: The 2 most common chemotherapy regimens used concurrently with thoracic radiation for patients with unresectable IIIA and IIIB non-small-cell lung cancer (NSCLC) are carboplatin-paclitaxel and cisplatin-etoposide. There are no prospective comparisons of these 2 regimens in this setting.

Objective: To conduct a systematic review of published trials to compare outcomes and toxic effects between cisplatin-etoposide and carboplatin-paclitaxel in patients with non-small-cell lung cancer receiving thoracic radiation.

Epidermal Growth Factor Receptor Mutated Advanced Non-Small Cell Lung Cancer: A Changing Treatment Paradigm.

Activating mutations in the epidermal growth factor receptor (EGFR) are present in approximately 15% of US patients with lung adenocarcinoma. EGFR tyrosine kinase inhibitors are associated with high response rate and progression-free survival for patients with non-small cell lung cancer with this genotype. Gefitinib, erlotinib, and afatinib are the EGFR tyrosine kinase inhibitors that are presently in clinical use.

Patient-derived xenografts faithfully replicated clinical outcome in a phase II co-clinical trial of arsenic trioxide in relapsed small cell lung cancer.

Background: SCLC has limited treatment options and inadequate preclinical models. Promising activity of arsenic trioxide (ASO) recorded in conventional preclinical models of SCLC supported the clinical evaluation of ASO in patients. We assessed the efficacy of ASO in relapsed SCLC patients and in corresponding patient-derived xenografts (PDX).

Adjuvant therapy for nonsmall cell lung cancer: recent advances and future perspectives.

Purpose Of Review: In this article, we discuss the emergence of adjuvant chemotherapy as the standard of care, the potential role of targeted and immune therapy in resected nonsmall cell lung cancer (NSCLC) patients, and the importance of ongoing clinical trials to further define the use of these agents as adjuvant therapy.

Recent Findings: Adjuvant chemotherapy after surgical resection provides modest improvements in cure rate, though recurrence of disease still occurs in a substantial proportion of patients. The advent of targeted and immune therapies has improved outcomes for patients with advanced stage NSCLC.

Early clearance of peripheral blood blasts predicts response to induction chemotherapy in acute myeloid leukemia.

Background: Early marrow blast clearance 14 days after induction chemotherapy is an independent prognostic indicator of outcomes in acute myeloid leukemia (AML).

Methods: We evaluated the relationship between time to peripheral blood blast clearance after induction and disease status as assessed by day 14 and day 30 marrow biopsies in 162 patients with AML. Day 6 after induction was the optimal cutoff point determined by a receiver operating characteristic analysis and was selected to divide patients into early blast clearance (EBC; ≤6 days; n = 119) and delayed blast clearance (DBC; >6 days; n = 43) groups.

Human immunodeficiency virus-associated lung cancer in the era of highly active antiretroviral therapy.

Background: Lung cancer is the leading cause of death among non-acquired immunodeficiency syndrome (AIDS)-defining malignancies. Because highly active antiretroviral therapy (HAART) has improved the survival of patients with human immunodeficiency virus (HIV), the authors evaluated lung cancer outcomes in the HAART era.

Methods: HIV-positive patients who were diagnosed with lung cancer at the authors' institution during the HAART era (1995-2008) were analyzed.

Lung cancer in HIV-positive patients.

Malignancies account for more than a third of all deaths in human immunodeficiency virus (HIV)-positive patients. Although acquired immunodeficiency syndrome-related mortality is decreasing with the introduction of effective antiretroviral therapy, the incidence of lung cancer in patients with HIV remains high. Lung cancer has now become the leading cause of mortality among the nonacquired immunodeficiency syndrome defining malignancies.

Combined inhibition of vascular endothelial growth factor and epidermal growth factor signaling in non-small-cell lung cancer therapy.

Elucidation of molecular pathways that promote malignancies has led to the identification of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) as key components involved in regulation of tumor proliferation and angiogenesis, respectively. Biologic agents that target these individual pathways have proven effective in treating patients with advanced non-small-cell lung cancer (NSCLC), adding to previously available therapies and often with fewer side effects. However, inhibition of a single molecular pathway does not account for alternate pathways or biologic adaptations that eventually lead to resistance.