Phase II Study of Defactinib (VS6063) in Patients With Tumors With Loss: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol U.

Purpose: The NCI-MATCH trial assigned patients with solid tumors, lymphomas, or multiple myeloma to targeted therapies on the basis of identified genetic alterations from tumor biopsies. In preclinical models, ()-inactivated tumors display sensitivity to focal adhesion kinase (FAK) inhibition. The EAY131-U subprotocol evaluated the efficacy of defactinib, a FAK inhibitor, in patients with -altered tumors.

Using Oncology Treatment Pathway Data to Evaluate Serious Illness Communication, Care Utilization, and End-of-Life Care for Patients With Cancer.

Purpose: Oncology treatment pathways provide decision support and encourage guideline adherence. Pathway data combined with electronic health record (EHR) data can identify patient populations with poor prognoses, low serious illness conversation (SIC) rates, and high acute care utilization that may benefit from targeted interventions.

Patients And Methods: We conducted a retrospective cohort analysis among adults with cancer treated at seven affiliated sites of the Dana-Farber Cancer Institute (DFCI) who had navigations within 21 treatment pathways between July 29, 2019, and March 8, 2023.

Early Findings on the Use of Clinical Pathways for Management of Unwarranted Variation in Cancer Care.

Clinical pathways have the potential to improve complex clinical decision-making in cancer care. The authors implemented pathways with customized content to assist oncologists to select treatments, aiming for an on-pathway rate of 70%-85%. Treatment decisions were captured as on or off pathway, and metrics were shared monthly with users.

Randomized Phase II Trial of Seribantumab in Combination with Erlotinib in Patients with EGFR Wild-Type Non-Small Cell Lung Cancer.

Background: Seribantumab (MM-121) is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3 () to block heregulin ()-mediated signaling and induce receptor downregulation. This open-label, randomized phase 1/2 study evaluated safety and efficacy of seribantumab plus erlotinib in advanced non-small cell lung cancer (NSCLC). Here, we report the activity of seribantumab plus erlotinib, versus erlotinib alone, in patients with wild-type tumors and describe the potential predictive power of HRG.

Implementation to Optimization: A Tailored, Data-Driven Approach to Improve Provider Efficiency and Confidence in Use of the Electronic Medical Record.

Purpose: Nine months after the implementation of a new electronic medical record (EMR) system at a single institution, physicians (MDs), nurse practitioners (NPs), and physician assistants (PAs) expressed frustration with its use. We aimed to test if an individually tailored training approach reduced time spent with the EMR and increased confidence.

Materials And Methods: Two hours of training were conducted in a one-on-one manner with a trainer.

Lung Cancer Screening, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology.

Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. Early detection of lung cancer is an important opportunity for decreasing mortality. Data support using low-dose computed tomography (LDCT) of the chest to screen select patients who are at high risk for lung cancer.

Cost and Survival Analysis Before and After Implementation of Dana-Farber Clinical Pathways for Patients With Stage IV Non-Small-Cell Lung Cancer.

Purpose: Increasing costs and medical complexity are significant challenges in modern oncology. We explored the use of clinical pathways to support clinical decision making and manage resources prospectively across our network.

Materials And Methods: We created customized lung cancer pathways and partnered with a commercial vendor to provide a Web-based platform for real-time decision support and post-treatment data aggregation.

Radiologic-pathologic correlation of response to chemoradiation in resectable locally advanced NSCLC.

Objectives: Accurate assessment of tumor response to chemoradiation has the potential to guide clinical decision-making regarding surgical resection and/or dose escalation for patients. Early assessment has implications for Optimal local therapy for operable locally advanced non-small cell lung cancer (LA-NSCLC) is controversial. This study evaluated quantitative CT-based tumor measurements to predict pathologic response.

A Prospective Evaluation of Circulating Tumor Cells and Cell-Free DNA in EGFR-Mutant Non-Small Cell Lung Cancer Patients Treated with Erlotinib on a Phase II Trial.

Purpose: Genotype-directed therapy is the standard of care for advanced non-small cell lung cancer (NSCLC), but obtaining tumor tissue for genotyping remains a challenge. Circulating tumor cell (CTC) or cell-free DNA (cfDNA) analysis may allow for noninvasive evaluation. This prospective trial evaluated CTCs and cfDNA in EGFR-mutant NSCLC patients treated with erlotinib until progression.

MET Exon 14 Mutations in Non-Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression.

Purpose: Non-small-cell lung cancers (NSCLCs) harboring mutations in MET exon 14 and its flanking introns may respond to c-Met inhibitors. We sought to describe the clinical, pathologic, and genomic characteristics of patients with cancer with MET exon 14 mutations.

Patients And Methods: We interrogated next-generation sequencing results from 6,376 cancers to identify those harboring MET exon 14 mutations.

Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs.

Introduction: Activating mutations in the epidermal growth factor receptor gene (EGFR) predict for prolonged progression-free survival in patients with advanced non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs) versus chemotherapy. Long-term survival outcomes, however, remain undefined. The objective of this study was to determine the 5-year survival in these patients and identify clinical factors associated with overall survival (OS).

Expression of PD-1 and Its Ligands, PD-L1 and PD-L2, in Smokers and Never Smokers with KRAS-Mutant Lung Cancer.

Introduction: Clinical responses to immune checkpoint blockade by anti-programmed cell death protein-1 (PD-1)/PD-L1 monoclonal antibodies in non-small-cell lung cancer (NSCLC) are associated with PD-L1 expression and smoking status. We aimed to determine the expression profile of PD-1 and its ligands, PD-L1 and PD-L2, in both smokers and never smokers patients with KRAS-mutant NSCLC.

Methods: We retrospectively analyzed the clinical and molecular characteristics of 114 KRAS-mutant NSCLC patients (84 smokers and 30 never smokers) and their clinical tumor samples for the expression of PD-1, PD-L1, and PD-L2 by immunohistochemistry (IHC).

Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer.

Purpose: Programmed death 1 is an immune checkpoint that suppresses antitumor immunity. Nivolumab, a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody, was active and generally well tolerated in patients with advanced solid tumors treated in a phase I trial with expansion cohorts. We report overall survival (OS), response durability, and long-term safety in patients with non-small-cell lung cancer (NSCLC) receiving nivolumab in this trial.

Delay of treatment change after objective progression on first-line erlotinib in epidermal growth factor receptor-mutant lung cancer.

Background: Erlotinib is a highly active epidermal growth factor receptor (EGFR) kinase inhibitor that is approved for first-line use in lung cancers harboring EGFR mutations. Anecdotal experience suggests that this drug may provide continued disease control after patients develop objective progression of disease (PD), although this has not been systematically studied to date.

Methods: Patients who had Response Evaluation Criteria In Solid Tumors-defined PD who were participating in 3 prospective trials of first-line erlotinib in advanced lung cancer were studied retrospectively, and the progression characteristics were compared between patients with and without EGFR-sensitizing mutations.

A phase I trial of high dose gefitinib for patients with leptomeningeal metastases from non-small cell lung cancer.

Introduction: There are few effective treatment options for leptomeningeal metastasis (LM) in non-small-cell lung cancer (NSCLC). This study assessed the feasibility of high-dose gefitinib in patients with LM from NSCLC harboring EGFR mutations or prior systemic response to EGFR-TKI.

Methods: This phase I open-label trial of a novel gefitinib dosing schedule employed a 3+3 design.

Immunohistochemical Loss of LKB1 Is a Biomarker for More Aggressive Biology in KRAS-Mutant Lung Adenocarcinoma.

Purpose: LKB1 loss is common in lung cancer, but no assay exists to efficiently evaluate the presence or absence of LKB1. We validated an IHC assay for LKB1 loss and determined the impact of LKB1 loss in KRAS-mutant non-small cell lung cancer (NSCLC).

Experimental Design: We optimized and validated an IHC assay for LKB1 (clone Ley37D/G6) using a panel of lung cancer cell lines and tumors with known LKB1 mutations, including 2 patients with Peutz-Jeghers syndrome (PJS) who developed lung adenocarcinoma.

Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival.

Objective: Interstitial lung diseases are associated with increased risk of lung cancer. The prevalence of ILA at diagnosis of advanced non-small-cell lung cancer (NSCLC) and its impact on overall survival (OS) remain to be investigated.

Materials And Method: The study included 120 treatment-naïve stage IV NSCLC patients (53 males, 67 females).

Lung cancer screening, version 1.2015: featured updates to the NCCN guidelines.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Lung Cancer Screening provide recommendations for selecting individuals for lung cancer screening, and for evaluation and follow-up of nodules found during screening, and are intended to assist with clinical and shared decision-making. These NCCN Guidelines Insights focus on the major updates to the 2015 NCCN Guidelines for Lung Cancer Screening, which include a revision to the recommendation from category 2B to 2A for one of the high-risk groups eligible for lung cancer screening. For low-dose CT of the lung, the recommended slice width was revised in the table on "Low-Dose Computed Tomography Acquisition, Storage, Interpretation, and Nodule Reporting.

Aggressive therapy for patients with non-small cell lung carcinoma and synchronous brain-only oligometastatic disease is associated with long-term survival.

Objectives: Optimal therapy for patients with non-small cell lung carcinoma (NSCLC) presenting with synchronous brain-only oligometastases (SBO) is not well defined. We sought to analyze the effect of differing therapeutic paradigms in this subpopulation.

Materials And Methods: We retrospectively analyzed NSCLC patients with 1-4 SBO diagnosed between 1/2000 and 1/2011 at our institution.

Definitive primary therapy in patients presenting with oligometastatic non-small cell lung cancer.

Purpose: Although palliative chemotherapy is the standard of care for patients with diagnoses of stage IV non-small cell lung cancer (NSCLC), patients with a small metastatic burden, "oligometastatic" disease, may benefit from more aggressive local therapy.

Methods And Materials: We identified 186 patients (26% of stage IV patients) prospectively enrolled in our institutional database from 2002 to 2012 with oligometastatic disease, which we defined as 5 or fewer distant metastatic lesions at diagnosis. Univariate and multivariable Cox proportional hazards models were used to identify patient and disease factors associated with improved survival.

Noninvasive detection of response and resistance in EGFR-mutant lung cancer using quantitative next-generation genotyping of cell-free plasma DNA.

Purpose: Tumor genotyping using cell-free plasma DNA (cfDNA) has the potential to allow noninvasive assessment of tumor biology, yet many existing assays are cumbersome and vulnerable to false-positive results. We sought to determine whether droplet digital PCR (ddPCR) of cfDNA would allow highly specific and quantitative assessment of tumor genotype.

Experimental Design: ddPCR assays for EGFR, KRAS, and BRAF mutations were developed using plasma collected from patients with advanced lung cancer or melanoma of a known tumor genotype.

Chemotherapy with Erlotinib or chemotherapy alone in advanced non-small cell lung cancer with acquired resistance to EGFR tyrosine kinase inhibitors.

Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer has an oncogene-addicted biology that confers sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Published data suggest that EGFR addiction persists after development of TKI acquired resistance, leading many clinicians to continue TKI with subsequent chemotherapy; however, this strategy has not been formally evaluated. Methods.

Volumetric tumor growth in advanced non-small cell lung cancer patients with EGFR mutations during EGFR-tyrosine kinase inhibitor therapy: developing criteria to continue therapy beyond RECIST progression.

Background: The objective of this study was to define the volumetric tumor growth rate in patients who had advanced nonsmall cell lung cancer (NSCLC) with sensitizing epidermal growth factor receptor (EGFR) mutations and had initially received treatment with EGFR-tyrosine kinase inhibitor (TKI) therapy beyond progression.

Methods: The study included 58 patients with advanced NSCLC who had sensitizing EGFR mutations treated with first-line gefitinib or erlotinib, had baseline computed tomography (CT) scans available that revealed a measurable lung lesion, had at least 2 follow-up CT scans during TKI therapy, and had experienced volumetric tumor growth. The tumor volume (in mm3) of the dominant lung lesion was measured on baseline and follow-up CT scans during therapy.