Randomized Trial of Afatinib Plus Cetuximab Versus Afatinib Alone for First-Line Treatment of -Mutant Non-Small-Cell Lung Cancer: Final Results From SWOG S1403.

Purpose: The irreversible ErbB family tyrosine kinase inhibitor (TKI) afatinib plus the EGFR monoclonal antibody cetuximab was previously shown to overcome resistance to EGFR TKIs. We studied whether the combination of afatinib plus cetuximab compared with afatinib alone would improve progression-free survival (PFS) in patients with treatment-naive -mutant non-small-cell lung cancer (NSCLC) by preventing or delaying resistance.

Methods: Patients with -mutant NSCLC without prior treatment of advanced disease were enrolled in this phase II, multicenter trial and randomly assigned to receive afatinib 40 mg orally daily plus cetuximab 500 mg/m intravenously every 2 weeks or afatinib alone.

Pembrolizumab for management of patients with NSCLC and brain metastases: long-term results and biomarker analysis from a non-randomised, open-label, phase 2 trial.

Background: We did a phase 2 trial of pembrolizumab in patients with non-small-cell lung cancer (NSCLC) or melanoma with untreated brain metastases to determine the activity of PD-1 blockade in the CNS. Interim results were previously published, and we now report an updated analysis of the full NSCLC cohort.

Methods: This was an open-label, phase 2 study of patients from the Yale Cancer Center (CT, USA).

Measuring the Impact of Academic Cancer Network Development on Clinical Integration, Quality of Care, and Patient Satisfaction.

Purpose: Many US academic centers have acquired community practices to expand their clinical care and research footprint. The objective of this assessment was to determine whether the acquisition and integration of community oncology practices by Yale/Smilow Cancer Hospital improved outcomes in quality of care, disease team integration, clinical trial accrual, and patient satisfaction at network practice sites.

Methods: We evaluated quality of care by testing the hypothesis that core Quality Oncology Practice Initiative measures at network sites that were acquired in 2012 were significantly different after their 2016 integration into the network.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 5.2018.

The NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) address all aspects of management for NSCLC. These NCCN Guidelines Insights focus on recent updates to the targeted therapy and immunotherapy sections in the NCCN Guidelines. For the 2018 update, a new section on biomarkers was added.

Do older patients with non-small cell lung cancer also benefit from first-line platinum-based doublet chemotherapy? Observations from a pooled analysis of 730 prospectively-treated patients (Alliance Study A151622).

Objective: This study sought to define the role of first-line platinum-based doublet chemotherapy in older patients with non-small cell lung cancer (NSCLC).

Materials And Methods: We analyzed three first-line NSCLC trials: CALGB 9730, CALGB 30203, and CALGB 30801, which tested carboplatin and paclitaxel; carboplatin and gemcitabine; and carboplatin with either pemetrexed or gemcitabine, respectively. Overall survival was the primary endpoint.

Time-to-Treatment-Failure and Related Outcomes Among 1000+ Advanced Non-Small Cell Lung Cancer Patients: Comparisons Between Older Versus Younger Patients (Alliance A151711).

Introduction: Time-to-treatment-failure (TTF) is the interval from chemotherapy initiation to premature discontinuation. We evaluated TTF based on age.

Methods: Pooled analyses were conducted with first-line chemotherapy trials for advanced NSCLC (CALGB 9730, 30203, and 30801).

Clinical Features and Management of Acquired Resistance to PD-1 Axis Inhibitors in 26 Patients With Advanced Non-Small Cell Lung Cancer.

Introduction: With expanding indications for programmed death 1 (PD-1) axis inhibitors in non-small cell lung cancer (NSCLC), acquired resistance (AR) to these therapies is increasingly being encountered. We sought to characterize clinical patterns of AR to PD-1 axis inhibitors in patients with advanced NSCLC, and evaluate subsequent outcome and management strategies for such patients.

Methods: Patients with NSCLC who developed AR to PD-1 axis inhibitor therapy initiated between December 2009 and February 2016 at one institution were identified and examined by clinical and radiographic features.

Randomized phase 2 study of tivantinib plus erlotinib versus single-agent chemotherapy in previously treated KRAS mutant advanced non-small cell lung cancer.

Background: KRAS mutations are identified in approximately 25% of non-small cell lung cancer (NSCLC) cases and are associated with resistance to currently available targeted therapies. The MET oncogene may be implicated in malignant progression of KRAS-mutant tumors. In a pre-specified subset analysis of KRAS mutant cancers in an earlier phase 2 study of erlotinib plus the oral MET inhibitor tivantinib, combination therapy was associated with substantial clinical benefit compared to erlotinib alone (progression-free survival [PFS] HR 0.

Development of Imminent Mortality Predictor for Advanced Cancer (IMPAC), a Tool to Predict Short-Term Mortality in Hospitalized Patients With Advanced Cancer.

Purpose: End-of-life care for patients with advanced cancer is aggressive and costly. Oncologists inconsistently estimate life expectancy and address goals of care. Currently available prognostication tools are based on subjective clinical assessment.

Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) focuses on targeted therapies and immunotherapies for metastatic NSCLC, because therapeutic recommendations are rapidly changing for metastatic disease. For example, new recommendations were added for atezolizumab, ceritinib, osimertinib, and pembrolizumab for the 2017 updates.

Preparing for Value-Based Payment: A Stepwise Approach for Cancer Centers.

Most cancer centers are ill-equipped to pursue value-based payment (VBP) because of limited information on their population's cost of care. Herein, we outline the stepwise approach used by Smilow Cancer Hospital at Yale-New Haven in our pursuit of better value care. First, we addressed institutional barriers.

NCCN Guidelines Insights: Malignant Pleural Mesothelioma, Version 3.2016.

These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category 1) for patients with MPM.

Management of EGFR Mutation-Positive Non-Small Cell Lung Cancer.

For appropriate treatment selection, the updated NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC) recommend broad molecular profiling for all patients with nonsquamous disease. Three different tyrosine kinase inhibitors (TKIs) are recommended as first-line treatment of EGFR mutation-positive NSCLC: gefitinib, erlotinib, and afatinib. Most patients whose disease responds will still experience progression, and the type of disease progression drives management.

Assessing Clinical Trial-Associated Workload in Community-Based Research Programs Using the ASCO Clinical Trial Workload Assessment Tool.

Purpose: Clinical research program managers are regularly faced with the quandary of determining how much of a workload research staff members can manage while they balance clinical practice and still achieve clinical trial accrual goals, maintain data quality and protocol compliance, and stay within budget. A tool was developed to measure clinical trial-associated workload, to apply objective metrics toward documentation of work, and to provide clearer insight to better meet clinical research program challenges and aid in balancing staff workloads. A project was conducted to assess the feasibility and utility of using this tool in diverse research settings.

Optimizing Treatment Risk and Benefit for Elderly Patients With Advanced Non-Small-Cell Lung Cancer: The Right Treatment for the Right Patient.

The Oncology Grand Rounds series is designed to place original reports published in theJournal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published inJournal of Clinical Oncology, to patients seen in their own clinical practice.

NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 4.2016.

These NCCN Guidelines Insights focus on recent updates in the 2016 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC; Versions 1-4). These NCCN Guidelines Insights will discuss new immunotherapeutic agents, such as nivolumab and pembrolizumab, for patients with metastatic NSCLC. For the 2016 update, the NCCN panel recommends immune checkpoint inhibitors as preferred agents (in the absence of contraindications) for second-line and beyond (subsequent) therapy in patients with metastatic NSCLC (both squamous and nonsquamous histologies).

Human bedside evaluation versus automatic responsiveness testing in epilepsy (ARTiE).

Evaluation of behavioral impairment during epileptic seizures is critical for medical decision making, including accurate diagnosis, recommendations for driving, and presurgical evaluation. We investigated the quality of behavioral testing during inpatient video-electroencephalography (EEG) monitoring at an established epilepsy center, and introduce a technical innovation that may improve clinical care. We retrospectively reviewed video-EEG data from 152 seizures in 33 adult or pediatric patients admitted for video-EEG monitoring.

Role of Chemoradiotherapy in Elderly Patients With Limited-Stage Small-Cell Lung Cancer.

Purpose: To investigate outcomes for elderly patients treated with chemotherapy (CT) alone versus chemoradiotherapy (CRT) in the modern era by using a large national database.

Patients And Methods: Elderly patients (age ≥ 70 years) with limited-stage small-cell lung cancer clinical stage I to III who received CT or CRT were identified in the National Cancer Data Base between 2003 and 2011. Hierarchical mixed-effects logistic regression with clustering by reporting facility was performed to identify factors associated with treatment selection.

The Treatment of Advanced Lung Cancer in the Elderly: The Role of a Comprehensive Geriatric Assessment and Doublet Chemotherapy.

The US lung cancer population is aging, the majority of which receive a diagnosis of incurable advanced non-small cell lung cancer (NSCLC). In US clinical oncology practice, elderly is defined as patients older than 70 years. Treatment of elderly patients with advanced NSCLC is complex.

Expectations in the care of lung cancer.

One of the main challenges oncologists face in the care of patients with lung cancer is the decision to incorporate new clinical trial data into routine clinical practice. Beyond the question of statistical significance, which is a more objective metric, are the results meaningful and applicable to a broader population? Furthermore, in an era of value care, do the results justify a potential increase in costs? This article discusses the main points that clinicians consider in their decision-making process and illustrates the arguments with real-life examples.

The spectrum of neuroendocrine tumors: histologic classification, unique features and areas of overlap.

Neuroendocrine neoplasms are diverse in terms of sites of origin, functional status, and degrees of aggressiveness. This review will introduce some of the common features of neuroendocrine neoplasms and will explore the differences in pathology, classification, biology, and clinical management between tumors of different anatomic sites, specifically, the lung, pancreas, and prostate. Despite sharing neuroendocrine differentiation and histologic evidence of the neuroendocrine phenotype in most organs, well-differentiated neuroendocrine tumors (WD-NETs) and poorly differentiated neuroendocrine carcinomas (PD-NECs) are two very different families of neoplasms.

Non-Small Cell Lung Cancer, Version 6.2015.

These NCCN Guidelines Insights focus on recent updates to the 2015 NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC). Appropriate targeted therapy is very effective in patients with advanced NSCLC who have specific genetic alterations. Therefore, it is important to test tumor tissue from patients with advanced NSCLC to determine whether they have genetic alterations that make them candidates for specific targeted therapies.

Treatment of Elderly Patients With Non-Small-Cell Lung Cancer: Results of an International Expert Panel Meeting of the Italian Association of Thoracic Oncology.

Most patients with non-small-cell lung cancer (NSCLC) are elderly, and age has important implications for their management and treatment. In May 2014, the Italian Association of Thoracic Oncology organized an International Experts Panel Meeting with the intent to review the available evidence regarding the treatment of elderly patients with NSCLC and to discuss the implications for clinical practice and future research in this field; this article summarizes the panelists' conclusions. All patients aged more than 70 years should receive an assessment of physiologic age, including mortality and toxicity prediction.

Non-small cell lung cancer, version 1.2015.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer (NSCLC) focuses on the principles of radiation therapy (RT), which include the following: (1) general principles for early-stage, locally advanced, and advanced/metastatic NSCLC; (2) target volumes, prescription doses, and normal tissue dose constraints for early-stage, locally advanced, and advanced/palliative RT; and (3) RT simulation, planning, and delivery. Treatment recommendations should be made by a multidisciplinary team, including board-certified radiation oncologists who perform lung cancer RT as a prominent part of their practice.

Generalizability of trial results to elderly Medicare patients with advanced solid tumors (Alliance 70802).

Background: In the United States, patients who enroll in chemotherapy trials seldom reflect the attributes of the general population with cancer, as they are often younger, more functional, and have less comorbidity. We compared survival following three chemotherapy regimens according to the setting in which care was delivered (ie, clinical trial vs usual care) to determine the generalizability of clinical trial results to unselected elderly Medicare patients.

Methods: Using SEER-Medicare data, we estimated survival for elderly patients (ie, age 65 years or older, n = 14097) with advanced pancreatic or lung cancer following receipt of one of three guideline-recommended first-line chemotherapy regimens.