Factors associated with time to EGFR TKI treatment in patients with non-squamous metastatic non-small-cell lung cancer.

Assess factors associated with EGFR TKI initiation among patients with metastatic non-small-cell lung cancer (mNSCLC). Medicare Part D patients diagnosed with non-squamous mNSCLC and starting an EGFR TKI within 1 year of diagnosis were selected from the Surveillance, Epidemiology and End Results (SEER)-Medicare database. Associations between patient characteristics and time from diagnosis to treatment initiation (time-to-treatment [TTT]) were analyzed.

Racial disparity in oncologic and quality-of-life outcomes in patients with locally advanced head and neck squamous cell carcinomas enrolled in a randomized phase 2 trial.

Background: To better understand patient-reported quality of life (PRQOL) for patients with head and neck cancer, PRQOL scores were collected in a clinical trial.

Methods: Patients were randomized to arm A (70 Gy of radiation with cisplatin) or arm B (70 Gy of radiation with cisplatin plus erlotinib at 150 mg daily). PRQOL scores were measured on days -7 (arm B only), 0, 30, and 180 with the University of Washington Quality of Life Questionnaire.

Phase II trial of eribulin mesylate in recurrent or metastatic salivary gland malignancies.

Background: This study examined the microtubule inhibitor eribulin in recurrent/metastatic salivary gland cancers (RMSGCs), a disease where no therapeutic standard exists.

Methods: This phase II clinical trial treated patients with progressive recurrent/metastatic salivary gland cancers with eribulin 1.4 mg/m i.

A phase I study of pazopanib in combination with escalating doses of 131I in patients with well-differentiated thyroid carcinoma borderline refractory to radioiodine.

Objective: This trial was conducted to evaluate the ability of pazopanib to overcome therapeutic 131I resistance.

Materials, Methods And Patients: This phase 1 trial assesses the combination of pazopanib and escalating doses of radioiodine (131I) in patients with recurrent or metastatic thyroid cancer that are borderline or relatively iodine refractory. Radioiodine uptake scans were assessed post therapy and compared to historical pre-treatment scans.

Safety and activity of pembrolizumab in patients with locally advanced or metastatic urothelial cancer (KEYNOTE-012): a non-randomised, open-label, phase 1b study.

Background: PD-1 and its ligands are expressed in urothelial cancer, and findings have shown that inhibition of the PD-1 pathway has clinical benefit. We aimed to assess the safety and activity of an anti-PD-1 antibody pembrolizumab in patients with locally advanced or metastatic urothelial cancer.

Methods: This study was part of the non-randomised, multi-cohort, open-label, phase 1b KEYNOTE-012 basket trial.

Systemic therapy of brain metastases: non-small cell lung cancer, breast cancer, and melanoma.

Brain metastases (BM) occur frequently in many cancers, particularly non-small cell lung cancer (NSCLC), breast cancer, and melanoma. The development of BM is associated with poor prognosis and has an adverse impact on survival and quality of life. Commonly used therapies for BM such as surgery or radiotherapy are associated with only modest benefits.

Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study.

Background: Nivolumab has shown improved survival in the treatment of advanced non-small-cell lung cancer (NSCLC) previously treated with chemotherapy. We assessed the safety and activity of combination nivolumab plus ipilimumab as first-line therapy for NSCLC.

Methods: The open-label, phase 1, multicohort study (CheckMate 012) cohorts reported here were enrolled at eight US academic centres.

Harnessing the Immune System as a Therapeutic Tool in Virus-Associated Cancers.

Importance: There are at least 7 viruses implicated in the pathogenesis of 10% to 15% of all human cancers worldwide. Despite a high prevalence of infection with these viruses, only a minority of infected individuals develop a subsequent malignant tumor, underscoring the important role that host and environmental factors have in cancer development. This article reviews the mechanisms of viral carcinogenesis, with an emphasis on the viral evasion of the host immune system, and discusses how to harness the immune system effectively as a therapeutic tool in select cancers.

Phase 2 Study of Erlotinib in Combination With Linsitinib (OSI-906) or Placebo in Chemotherapy-Naive Patients With Non-Small-Cell Lung Cancer and Activating Epidermal Growth Factor Receptor Mutations.

Introduction: First-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment of advanced non-small-cell lung cancer with EGFR-activating mutations improves outcomes compared with chemotherapy, but resistance develops in most patients. Compensatory signaling through type 1 insulin-like growth factor 1 receptor (IGF-1R) may contribute to resistance; dual blockade of IGF-1R and EGFR may improve outcomes.

Patients And Methods: We performed a randomized, double-blind, placebo-controlled phase II study of linsitinib, a dual IGF-1R and insulin receptor tyrosine kinase inhibitor, plus erlotinib versus placebo plus erlotinib in chemotherapy-naive patients with EGFR-mutation positive, advanced non-small-cell lung cancer.

Lack of pharmacokinetic drug-drug interaction between ramucirumab and paclitaxel in a phase II study of patients with advanced malignant solid tumors.

Purpose: The objective of this phase II study was to evaluate pharmacokinetic interaction potential between ramucirumab and paclitaxel in patients with advanced cancer.

Methods: This study was designed to assess 2-way pharmacokinetic drug-drug interactions between ramucirumab and paclitaxel. Twenty-four patients participated in Part A, which consisted of a 2-week monotherapy period in which paclitaxel 80 mg/m(2) was administered on day 1, followed by a 4-week cycle of combination treatment with ramucirumab (8 mg/kg on days 1 and 15; paclitaxel on days 1, 8, and 15).

Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer.

Purpose: Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non-small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial.

Methods: Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol.

Nivolumab in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer.

Purpose: Nivolumab, a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody, has demonstrated improved survival in previously treated patients with advanced non-small-cell lung cancer (NSCLC). CheckMate 012, a phase I, multicohort study, was conducted to explore the safety and efficacy of nivolumab as monotherapy or combined with current standard therapies in first-line advanced NSCLC. Here, we report results for nivolumab plus platinum-based doublet chemotherapy (PT-DC).

Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial.

Background: Patients with recurrent or metastatic squamous cell carcinoma of the head and neck have few treatment options. We aimed to assess the safety, tolerability, and antitumour activity of pembrolizumab, a humanised anti-programmed death receptor 1 (PD-1) antibody, in patients with PD-L1-positive recurrent or metastatic squamous cell carcinoma of the head and neck.

Methods: This study was an open-label, multicentre, phase 1b trial of patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study.

Purpose: Immune checkpoint inhibition has been demonstrated to be an effective anticancer strategy. Several lines of evidence support the study of immunotherapy in triple-negative breast cancer (TNBC). We assessed the safety and antitumor activity of the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab in patients with advanced TNBC.

Coordinated Activation of Toll-Like Receptor8 (TLR8) and NLRP3 by the TLR8 Agonist, VTX-2337, Ignites Tumoricidal Natural Killer Cell Activity.

Unlabelled: VTX-2337 (USAN: motolimod) is a selective toll-like receptor 8 (TLR8) agonist, which is in clinical development as an immunotherapy for multiple oncology indications, including squamous cell carcinoma of the head and neck (SCCHN). Activation of TLR8 enhances natural killer cell activation, increases antibody-dependent cell-mediated cytotoxicity, and induces Th1 polarizing cytokines. Here, we show that VTX-2337 stimulates the release of mature IL-1β and IL-18 from monocytic cells through coordinated actions on both TLR8 and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome complex.

Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer.

Background: Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity.

Methods: In this randomized, open-label, international phase 3 study, we assigned patients with nonsquamous non-small-cell lung cancer (NSCLC) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival.

Targeted Therapy for Brain Metastases in EGFR-Mutated and ALK-Rearranged Non-Small-Cell Lung Cancer.

Approximately half of all patients with non-small-cell lung cancer (NSCLC) develop brain metastases (BM) during the course of their disease, leading to significant challenges in treatment. Molecular targeted tyrosine kinase inhibitors have proven effective for patients with activating mutations in the epidermal growth factor receptor gene and chromosomal rearrangements involving the anaplastic lymphoma kinase gene. Despite their efficacy in systemic disease control, their effectiveness in patients with BM is not well established.

The Evolving Role of Immune Checkpoint Inhibitors in Cancer Treatment.

Unlabelled: Traditional treatment modalities for advanced cancer (radiotherapy, chemotherapy, or targeted agents) act directly on tumors to inhibit or destroy them. Along with surgery, these modalities are predominantly palliative, with toxicity and only modest improvements in survival in patients with advanced solid tumors. Accordingly, long-term survival rates for most patients with advanced cancer remain low, thus there is a need for cancer treatments with favorable benefit and toxicity profiles that can potentially result in long-term survival.

Ceritinib in ALK-rearranged non-small-cell lung cancer.

Background: Non-small-cell lung cancer (NSCLC) harboring the anaplastic lymphoma kinase gene (ALK) rearrangement is sensitive to the ALK inhibitor crizotinib, but resistance invariably develops. Ceritinib (LDK378) is a new ALK inhibitor that has shown greater antitumor potency than crizotinib in preclinical studies.

Methods: In this phase 1 study, we administered oral ceritinib in doses of 50 to 750 mg once daily to patients with advanced cancers harboring genetic alterations in ALK.

Adjuvant Radiotherapy for Stages II and III Resected Thymoma: A Single-institutional Experience.

Introduction: The role of adjuvant radiation for Masaoka stages II and III thymoma remains controversial. The aim of this study was to evaluate the clinical benefit of radiation therapy for resected stages II and III thymoma patients.

Methods: We retrospectively reviewed the medical records of 175 thymoma patients treated from July 1996 to January 2013 at University of Washington Medical Center; 88 patients with adequate follow-up and who met histologic criteria were included.

Sunitinib combined with pemetrexed and carboplatin in patients with advanced solid malignancies--results of a phase I dose-escalation study.

Objectives: The maximum tolerated dose (MTD) and overall safety of sunitinib plus pemetrexed and carboplatin was determined in patients with advanced solid malignancies.

Methods: In this phase I dose-escalation study, patients received oral sunitinib on a continuous daily dosing (CDD) schedule (37.5 mg/day) or Schedule 2/1 (2 weeks on treatment, 1 week off treatment; 37.

Neutron radiotherapy for adenoid cystic carcinoma of the lacrimal gland.

Purpose: Lacrimal gland adenoid cystic carcinomas are rare, aggressive orbital tumors that share histopathologic similarities with salivary gland malignancies. Neutron radiotherapy may be useful for treatment due to its high biological effectiveness for salivary malignancies.

Methods: The authors retrospectively reviewed the outcomes for 11 lacrimal gland adenoid cystic carcinoma patients treated with neutrons from 1988 to 2011.