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Targeted/Emerging Therapies for Metastatic Non–Small Cell Lung Cancer

Leora Horn

At one time, histology alone guided treatment decisions in non–small cell lung cancer (NSCLC), but now molecular diagnostics help to categorize patients with lung cancer by driver mutations. This additional information arms oncologists with the keys to selecting the right targeted agent with the best chance of success for different subgroups of patients with NSCLC. During her presentation at the NCCN 20th Annual Conference, Dr. Leora Horn focused attention on both approved and emerging therapies in metastatic disease that target an assortment of molecular subsets, such as EGFR mutations, ALK rearrangements, ROS1 rearrangements, and BRAF mutations.

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Advances in the Treatment of Non-Small Cell Lung Cancer

Leora Horn

Clinical trial data continue to emerge on treatments in advanced non-small cell lung cancer (NSCLC), supporting the strategy that histology and molecular driver mutations should guide treatment selection. During her presentation at the NCCN 19th Annual Conference, Dr. Leora Horn highlighted 3 specific areas in which the 2014 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for NSCLC focus attention: updates on the assortment of chemotherapy options, targeted therapies and how acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors appears to have become the catalyst of the development of newer-generations of agents, and the revisited role of newer immunotherapeutic options.

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Targeting Angiogenesis in Advanced Non-Small Cell Lung Cancer

Philip E. Lammers and Leora Horn

Lung cancer is the leading cause of cancer-related mortality in the United States. Over the past 40 years, treatments with standard chemotherapy agents have not resulted in substantial improvements in long-term survival for patients with advanced lung cancer. Therefore, new targets have been sought, and angiogenesis is a promising target for non-small cell lung cancer (NSCLC). Bevacizumab, a monoclonal antibody targeted against the vascular endothelial growth factor, is the only antiangiogenic agent currently recommended by NCCN for the treatment of advanced NSCLC. However, several antibody-based therapies and multitargeted tyrosine kinase inhibitors are currently under investigation for the treatment of patients with NSCLC. This article summarizes the available clinical trial data on the efficacy and safety of these agents in patients with advanced lung cancer.

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Management of EGFR Mutation–Positive Non–Small Cell Lung Cancer

Rogerio A. Lilenbaum and Leora A. Horn

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. Systemic progression requires switching TKI treatment, whereas patients with oligoprogression and central nervous system progression may have their new lesions treated but continue on their TKI. A new third-generation TKI has been approved and others are currently under development, and new combinations of these drugs with a VEGFR inhibitor offer promise to improve outcomes.

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A Patient With Metastatic Lung Adenocarcinoma Harboring Concurrent EGFR L858R, EGFR Germline T790M, and PIK3CA Mutations: The Challenge of Interpreting Results of Comprehensive Mutational Testing in Lung Cancer

Philip E. Lammers, Christine M. Lovly, and Leora Horn

Mutational testing has moved to the forefront as an integral component in the management of patients with non-small cell lung cancer (NSCLC). Currently 3 targeted therapies (erlotinib, afatinib, and crizotinib) are approved by the FDA to treat patients with specific genetic abnormalities in NSCLC. As mutational screening expands to include a greater number of genes, the results will become more difficult to interpret, particularly if mutations are found in multiple genes or genes that are not actionable at the time of testing. This case report summarizes the diagnosis and treatment of a patient with NSCLC that harbored multiple potentially targetable driver mutations. It also discusses the current NCCN Clinical Practice Guidelines in Oncology for mutational testing in NSCLC and the inherent difficulties with interpreting mutational results when multiple mutations are found in a single gene or across multiple genes.

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Making the Grade: The Impact of Low-Grade Toxicities on Patient Preference for Treatment With Novel Agents

Emily H. Castellanos, Sheau-chiann Chen, Hillary Drexler, and Leora Horn

Background: Targeted therapies have shown clinical benefit in the treatment of solid tumors. The toxicity profiles and treatment duration and schedule of these agents differ considerably from those of traditional chemotherapy. Many studies of targeted therapies report sizeable numbers of grade 1 or 2 toxicities. We sought to determine whether anticipation of low-grade toxicities and treatment logistics impact patient willingness to undergo therapy. Patients and Methods: A total of 209 patients with cancer (101 lung and 108 breast) were surveyed at the Vanderbilt-Ingram Cancer Center regarding willingness to comply with treatment based on anticipated efficacy, dosing convenience, and toxicity profiles. All toxicities were Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 1 and 2. Willingness to comply with treatment depending on toxicity, anticipated benefit, cancer type, and dosing convenience was compared. Results: A substantial number of patients (2.9%–48.8%, depending on the toxicity described) professed unwillingness to undergo treatment because of anticipated grade 1 and 2 toxicities. Gastrointestinal and constitutional toxicities had a stronger negative impact on patient willingness to undergo therapy than dermatologic toxicity. Patients with lung cancer were significantly more likely to accept dermatologic and gastrointestinal toxicities than those with breast cancer. Willingness to tolerate toxicities correlated with expected benefit in terms of life expectancy and chance of cure. Lengthy travel distance for treatment negatively impacted willingness to undergo treatment. Conclusions: Anticipation of low-grade toxicities and dosing inconvenience negatively impacts patient willingness to be treated, which may affect adherence and therapeutic outcomes from therapy. Long-term tolerability should be considered when developing and assessing the impact of novel agents.

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Low Provider Knowledge Is Associated With Less Evidence-Based Lung Cancer Screening

Jennifer A. Lewis, Heidi Chen, Kathryn E. Weaver, Lucy B. Spalluto, Kim L. Sandler, Leora Horn, Robert S. Dittus, Pierre P. Massion, Christianne L. Roumie, and Hilary A. Tindle

Background: Despite widespread recommendation and supportive policies, screening with low-dose CT (LDCT) is incompletely implemented in the US healthcare system. Low provider knowledge of the lung cancer screening (LCS) guidelines represents a potential barrier to implementation. Therefore, we tested the hypothesis that low provider knowledge of guidelines is associated with less provider-reported screening with LDCT. Patients and Methods: A cross-sectional survey was performed in a large academic medical center and affiliated Veterans Health Administration in the Mid-South United States that comprises hospital and community-based practices. Participants included general medicine providers and specialists who treat patients aged >50 years. The primary exposure was LCS guideline knowledge (US Preventive Services Task Force/Centers for Medicare & Medicaid Services). High knowledge was defined as identifying 3 major screening eligibility criteria (55 years as initial age of screening eligibility, smoking status as current or former smoker, and smoking history of ≥30 pack-years), and low knowledge was defined as not identifying these 3 criteria. The primary outcome was self-reported LDCT order/referral within the past year, and the secondary outcome was screening chest radiograph. Multivariable logistic regression evaluated the adjusted odds ratio (aOR) of screening by knowledge. Results: Of 625 providers recruited, 407 (65%) responded, and 378 (60.5%) were analyzed. Overall, 233 providers (62%) demonstrated low LCS knowledge, and 224 (59%) reported ordering/referring for LDCT. The aOR of ordering/referring LDCT was less among providers with low knowledge (0.41; 95% CI, 0.24–0.71) than among those with high knowledge. More providers with low knowledge reported ordering screening chest radiographs (aOR, 2.7; 95% CI, 1.4–5.0) within the past year. Conclusions: Referring provider knowledge of LCS guidelines is low and directly proportional to the ordering rate for LDCT in an at-risk US population. Strategies to advance evidence-based LCS should incorporate provider education and system-level interventions to address gaps in provider knowledge.

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Identification and Characterization of Avoidable Hospital Admissions in Patients With Lung Cancer

Eric M. Lander, Xuanyi Li, Li-Ching Huang, Amanda S. Cass, Wade T. Iams, Emily A. Skotte, Jennifer G. Whisenant, Robert A. Ramirez, Sally J. York, Travis J. Osterman, Jennifer A. Lewis, Christine M. Lovly, Yu Shyr, and Leora Horn

Background: More than 50% of patients with lung cancer are admitted to the hospital while receiving treatment, which is a burden to patients and the healthcare system. This study characterizes the risk factors and outcomes of patients with lung cancer who were admitted to the hospital. Methods: A multidisciplinary oncology care team conducted a retrospective medical record review of patients with lung cancer admitted in 2018. Demographics, disease and admission characteristics, and end-of-life care utilization were recorded. Following a multidisciplinary consensus review process, admissions were determined to be either “avoidable” or “unavoidable.” Generalized estimating equation logistic regression models assessed risks and outcomes associated with avoidable admissions. Results: In all, 319 admissions for 188 patients with a median age of 66 years (IQR, 59–74 years) were included. Cancer-related symptoms accounted for 65% of hospitalizations. Common causes of unavoidable hospitalizations were unexpected disease progression causing symptoms, chronic obstructive pulmonary disease exacerbation, and infection. Of the 47 hospitalizations identified as avoidable (15%), the median overall survival was 1.6 months compared with 9.7 months (hazard ratio, 2.07; 95% CI, 1.34–3.19; P<.001) for unavoidable hospitalizations. Significant reasons for avoidable admissions included cancer-related pain (P=.02), hypervolemia (P=.03), patient desire to initiate hospice services (P=.01), and errors in medication reconciliation or distribution (P<.001). Errors in medication management caused 26% of the avoidable hospitalizations. Of admissions in patients receiving immunotherapy (n=102) or targeted therapy (n=44), 9% were due to adverse effects of treatment. Patients receiving immunotherapy and targeted therapy were at similar risk of avoidable hospitalizations compared with patients not receiving treatment (P=.3 and P=.1, respectively). Conclusions: We found that 15% of hospitalizations among patients with lung cancer were potentially avoidable. Uncontrolled symptoms, delayed implementation of end-of-life care, and errors in medication reconciliation were associated with avoidable inpatient admissions. Symptom management tools, palliative care integration, and medication reconciliations may mitigate hospitalization risk.

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Small Cell Lung Cancer

Gregory P. Kalemkerian, Wallace Akerley, Paul Bogner, Hossein Borghaei, Laura QM Chow, Robert J. Downey, Leena Gandhi, Apar Kishor P. Ganti, Ramaswamy Govindan, John C. Grecula, James Hayman, Rebecca Suk Heist, Leora Horn, Thierry Jahan, Marianna Koczywas, Billy W. Loo Jr, Robert E. Merritt, Cesar A. Moran, Harvey B. Niell, Janis O’Malley, Jyoti D. Patel, Neal Ready, Charles M. Rudin, Charles C. Williams Jr, Kristina Gregory, and Miranda Hughes

Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted.

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Small Cell Lung Cancer

Gregory P. Kalemkerian, Wallace Akerley, Paul Bogner, Hossein Borghaei, Laura Chow, Robert J. Downey, Leena Gandhi, Apar Kishor P. Ganti, Ramaswamy Govindan, John C. Grecula, James Hayman, Rebecca Suk Heist, Leora Horn, Thierry M. Jahan, Marianna Koczywas, Cesar A. Moran, Harvey B. Niell, Janis O'Malley, Jyoti D. Patel, Neal Ready, Charles M. Rudin, and Charles C. Williams Jr.