Impact of Socioeconomic Factors on Overall Survival in SCLC.

Objectives: To determine how the incidence and demographics of SCLC have changed over time and to evaluate whether patient demographics, disease presentation, and treatment characteristics affect patient outcomes.

Methods: We identified patients with SCLC in the National Cancer Database from 2004 to 2016. Differences in demographics, disease, and treatment characteristics were assessed by year of diagnosis using chi-square test.

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC.

Introduction: In cohort G of KEYNOTE-021 (NCT02039674), first-line pembrolizumab plus pemetrexed-carboplatin significantly improved the objective response rate and progression-free survival versus chemotherapy alone with manageable toxicity in advanced nonsquamous NSCLC. We report the long-term outcomes from this study.

Methods: Patients with previously untreated advanced nonsquamous NSCLC without sensitizing EGFR or ALK alterations were randomly assigned 1:1 to receive open-label pemetrexed 500 mg/m plus carboplatin at area under the concentration-time curve of 5 mg/mL/min (four cycles) with or without pembrolizumab 200 mg (up to 2 years), with optional pemetrexed maintenance, each administered every 3 weeks.

Nab-paclitaxel in older patients with non-small cell lung cancer who have developed disease progression after platinum-based doublet chemotherapy.

Background: The selection of later-line treatment for older patients with AJCC (version 7) stage IV non-small cell lung cancer (NSCLC) remains controversial. Nanoparticle albumin-bound (nab)-paclitaxel is approved with carboplatin for the first-line treatment of patients with NSCLC and subgroup analysis of phase 3 data has suggested superior survival in older patients.

Methods: The authors conducted a phase 2 study of nab-paclitaxel in 42 patients aged ≥70 years who had been treated previously with a platinum doublet regimen; patients also could have received a PD-1 inhibitor.

Clinical Outcomes of the HIV Protease Inhibitor Nelfinavir With Concurrent Chemoradiotherapy for Unresectable Stage IIIA/IIIB Non-Small Cell Lung Cancer: A Phase 1/2 Trial.

Importance: Local failure after chemoradiotherapy (CT-RT) significantly contributes to mortality in patients with locally advanced non-small cell lung cancer (LA-NSCLC). One approach to improve local control is through targeted radiosensitization of the tumor.

Objective: To evaluate the dose-limiting toxic effects, maximally tolerated dose, and recommended phase 2 dose of the protease inhibitor nelfinavir mesylate, administered concurrently with CT-RT in patients with LA-NSCLC, and, in the phase 2 portion of the study, to estimate the objective response rate, local and distant failure rates, and overall survival.

Pembrolizumab in combination with ipilimumab as second-line or later therapy for advanced non-small-cell lung cancer: KEYNOTE-021 cohorts D and H.

Objectives: Combination immunotherapy may result in improved antitumor activity compared with single-agent treatment. We report results from dose-finding and dose-expansion cohorts of the phase 1/2 KEYNOTE-021 study that evaluated combination therapy with anti‒programmed death 1 (PD-1) antibody pembrolizumab plus anti‒cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in patients with previously treated advanced non-small-cell lung cancer (NSCLC).

Materials And Methods: Eligibility criteria stipulated histologically/cytologically confirmed advanced NSCLC and treatment failure on ≥1 prior systemic therapy (platinum-based chemotherapy or targeted therapy for patients with EGFR/ALK aberrations).

Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non-small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study.

Objectives: Platinum-based chemotherapy for advanced non-small-cell lung cancer (NSCLC) has modest benefit overall, but has the potential to amplify immune responses. In cohorts A-C of the multicohort phase 1/2 study KEYNOTE-021 (Clinicaltrials.gov, NCT02039674), we evaluated combinations of platinum-doublet chemotherapy with the anti-programmed death 1 monocloncal antibody pembrolizumab.

Precision Oncology in Solid Tumors: A Longitudinal Tertiary Care Center Experience.

Purpose: Precision oncology is widely discussed, but cohort studies are limited. We previously reported our prospective experience of precision oncology in solid tumors, and here we report our longitudinal experience, focusing on therapeutic impact.

Patients And Methods: We conducted a retrospective review of 600 consecutive patients seen at Cleveland Clinic from 2013 to 2016 for treatment of incurable solid tumor malignancies for whom tumor genomic profiling was ordered using FoundationOne (Cambridge, MA).

Post-treatment changes in hematological parameters predict response to nivolumab monotherapy in non-small cell lung cancer patients.

Background: The absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute monocyte count (AMC) and neutrophil to lymphocyte ratio (NLR) are known markers of inflammation. We evaluated whether ANC, ALC, AMC and NLR, both before and after treatment with nivolumab, are indicative markers of overall survival (OS) and evaluated change in NLR as a predictive marker of response in non -small cell lung cancer (NSCLC) patients treated with nivolumab.

Methods: A total of 109 patients with advanced NSCLC treated with nivolumab were included.

24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non-Small Cell Lung Cancer.

Introduction: Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the primary analysis (median follow-up time 10.6 months), pembrolizumab significantly improved objective response rate (ORR) and progression-free survival (PFS); the hazard ratio (HR) for overall survival (OS) was 0.

Analysis of Origins of Admission for Solid Tumor Oncology Inpatients: Disease Severity and Outcomes.

Purpose: Hospital transfers may affect clinical outcomes. Evaluation of admission by source of transfer, time of admission, and provider type may identify opportunities to improve inpatient outcomes.

Methods: We reviewed charts of patients admitted to the solid tumor oncology service between July and December 2014 from the Cleveland Clinic Foundation (CCF) Main Campus emergency department (ED), CCF Regional EDs, outside hospital (OSH) ED, OSH inpatient services, and CCF outpatient clinics.

The evolution of the diminishing role of extrapleural pneumonectomy in the surgical management of malignant pleural mesothelioma.

Malignant pleural mesothelioma is an uncommon and aggressive thoracic malignancy that is rarely curable, even when multimodality therapy is used. Systemic chemotherapy is the primary treatment for the majority of patients with this disease; however, surgical resection may benefit a subset of patients with early-stage disease. The surgical approach that offers the best outcomes remains an area of controversy, with data from retrospective comparisons being the only guide.

Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study.

Background: Limited evidence exists to show that adding a third agent to platinum-doublet chemotherapy improves efficacy in the first-line advanced non-small-cell lung cancer (NSCLC) setting. The anti-PD-1 antibody pembrolizumab has shown efficacy as monotherapy in patients with advanced NSCLC and has a non-overlapping toxicity profile with chemotherapy. We assessed whether the addition of pembrolizumab to platinum-doublet chemotherapy improves efficacy in patients with advanced non-squamous NSCLC.

Analysis of the Relationship Between Response to Chemotherapy and Response to Radiation Therapy in Patients With Non-Small Cell Lung Cancer Receiving Sequential Treatment.

Objectives: We examine whether induction chemotherapy response predicts thoracic radiotherapy response in locally advanced or oligometastatic non-small cell lung cancer.

Materials And Methods: Between January 2001 to August 2010, 25 consecutive patients were identified who received systemic dose chemotherapy followed by definitive thoracic radiotherapy alone. All patients had measurable disease after chemotherapy that was evaluable for response to radiotherapy.

Pilot and Feasibility Trial Evaluating Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery of Adenovirus-IFNα Combined with Chemotherapy.

Purpose: "In situ vaccination" using immunogene therapy has the ability to induce polyclonal antitumor responses directed by the patient's immune system.

Experimental Design: Patients with unresectable malignant pleural mesothelioma (MPM) received two intrapleural doses of a replication-defective adenoviral vector containing the human IFNα2b gene (Ad.IFN) concomitant with a 14-day course of celecoxib followed by chemotherapy.

Reduction of Inappropriate Prophylactic Pegylated Granulocyte Colony-Stimulating Factor Use for Patients With Non-Small-Cell Lung Cancer Who Receive Chemotherapy: An ASCO Quality Training Program Project of the Cleveland Clinic Taussig Cancer Institute.

Purpose: Routine prophylactic pegylated granulocyte colony-stimulating factor (pGCSF) administration for patients receiving chemotherapy regimens associated with low risk (< 10%) for neutropenic fever (LRNF) is not recommended. Inappropriate use of pGCSF increases patient morbidity and health care costs.

Methods: A multidisciplinary team reviewed the charts of patients with non-small-cell lung cancer (NSCLC) at the Taussig Cancer Institute in whom a new chemotherapy regimen was initiated from April through November 2013.

Prospective Clinical Study of Precision Oncology in Solid Tumors.

Systematic studies evaluating clinical benefit of tumor genomic profiling are lacking. We conducted a prospective study in 250 patients with select solid tumors at the Cleveland Clinic. Eligibility required histopathologic diagnosis, age of 18 years or older, Eastern Cooperative Oncology Group performance status 0-2, and written informed consent.

Current issues in malignant pleural mesothelioma evaluation and management.

Malignant pleural mesothelioma (MPM) is an uncommon disease most often associated with occupational asbestos exposure and is steadily increasing in worldwide incidence. Patients typically present at an older age, with advanced clinical stage and other medical comorbidities, making management quite challenging. Despite great efforts, the prognosis of MPM remains poor, especially at progression after initial treatment.

Immunological effects of the TGFβ-blocking antibody GC1008 in malignant pleural mesothelioma patients.

We evaluated a neutralizing anti-TGFβ antibody (GC1008) in cancer patients with malignant pleura mesothelioma (MPM). The goal of this study was to assess immunoregulatory effects in relation to clinical safety and clinical response. Patients with progressive MPM and 1-2 prior systemic therapies received GC1008 at 3mg/kg IV over 90 min every 21 d as part of an open-label, two-center Phase II trial.

Impact of PET staging in limited-stage small-cell lung cancer.

Introduction: Although positron emission tomography computed tomography (PET-CT) has been widely used for small-cell lung cancer (SCLC) staging, no study has examined the clinical impact of PET staging in limited-stage (LS) SCLC.

Methods: We identified patients with LS-SCLC treated definitively with concurrent chemoradiation. Outcomes were assessed using the Kaplan-Meier approach, Cox regression, and competing risks method.

Multicenter, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma.

Purpose: Gemcitabine plus cisplatin is active in malignant mesothelioma (MM), although single-arm phase II trials have reported variable outcomes. Vascular endothelial growth factor (VEGF) inhibitors have activity against MM in preclinical models. We added the anti-VEGF antibody bevacizumab to gemcitabine/cisplatin in a multicenter, double-blind, placebo-controlled randomized phase II trial in patients with previously untreated, unresectable MM.

Phase 2 trial of maintenance bevacizumab alone after bevacizumab plus pemetrexed and carboplatin in advanced, nonsquamous nonsmall cell lung cancer.

Background: The authors performed a phase 2 study of bevacizumab plus pemetrexed and carboplatin followed by maintenance bevacizumab in patients with advanced, nonsquamous nonsmall cell lung cancer.

Methods: Previously untreated patients with advanced, nonsquamous nonsmall cell lung cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1 received bevacizumab 15 mg/kg, pemetrexed 500 mg/m(2) and carboplatin at an area under the concentration-time curve of 6 intravenously on day 1 every 21 days. Responding or stable patients who completed 6 cycles then received bevacizumab maintenance every 21 days until disease progression.

A phase I trial of the HIV protease inhibitor nelfinavir with concurrent chemoradiotherapy for unresectable stage IIIA/IIIB non-small cell lung cancer: a report of toxicities and clinical response.

Background: The objective of this phase I trial was to determine dose-limiting toxicities (DLT) and the maximally tolerated dose of the radiosensitizer Nelfinavir in combination with concurrent chemoradiotherapy in locally advanced non-small cell lung cancer (NSCLC).

Methods: Nelfinavir (dose level 1: 625 mg orally [PO] twice a day; dose level 2: 1250 mg PO twice a day) was administered for 7 to 14 days before and concurrently with concurrent chemoradiotherapy to patients with biopsy confirmed IIIA or IIIB unresectable NSCLC. Five patients were treated at dose level 1; eight patients were treated at dose level 2.

Photodynamic therapy for the treatment of non-small cell lung cancer.

Photodynamic therapy is increasingly being utilized to treat thoracic malignancies. For patients with early-stage non-small cell lung cancer, photodynamic therapy is primarily employed as an endobronchial therapy to definitely treat endobronchial, roentgenographically occult, or synchronous primary carcinomas. As definitive monotherapy, photodynamic therapy is most effective in treating bronchoscopically visible lung cancers ≤1 cm with no extracartilaginous invasion.