Research Spotlight

Traina, T. A., K. Miller, D. A. Yardley, J. Eakle, L. S. Schwartzberg, J. O’Shaughnessy, W. Gradishar, P. Schmid, E. Winer, C. Kelly, R. Nanda, A. Gucalp, A. Awada, L. Garcia-Estevez, M. E. Trudeau, J. Steinberg, H. Uppal, I. C. Tudor, A. Peterson and J. Cortes (2018). “Enzalutamide for the Treatment of Androgen Receptor-Expressing Triple-Negative Breast Cancer.” J Clin Oncol 36(9): 884-890.

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Purpose Studies suggest that a subset of patients with triple-negative breast cancer (TNBC) have tumors that express the androgen receptor (AR) and may benefit from an AR inhibitor. This phase II study evaluated the antitumor activity and safety of enzalutamide in patients with locally advanced or metastatic AR-positive TNBC. Patients and Methods Tumors were tested for AR with an immunohistochemistry assay optimized for breast cancer; nuclear AR staining > 0% was considered positive. Patients received enzalutamide 160 mg once per day until disease progression. The primary end point was clinical benefit rate (CBR) at 16 weeks. Secondary end points included CBR at 24 weeks, progression-free survival, and safety. End points were analyzed in all enrolled patients (the intent-to-treat [ITT] population) and in patients with one or more postbaseline assessment whose tumor expressed >/= 10% nuclear AR (the evaluable subgroup). Results Of 118 patients enrolled, 78 were evaluable. CBR at 16 weeks was 25% (95% CI, 17% to 33%) in the ITT population and 33% (95% CI, 23% to 45%) in the evaluable subgroup. Median progression-free survival was 2.9 months (95% CI, 1.9 to 3.7 months) in the ITT population and 3.3 months (95% CI, 1.9 to 4.1 months) in the evaluable subgroup. Median overall survival was 12.7 months (95% CI, 8.5 months to not yet reached) in the ITT population and 17.6 months (95% CI, 11.6 months to not yet reached) in the evaluable subgroup. Fatigue was the only treatment-related grade 3 or higher adverse event with an incidence of > 2%. Conclusion Enzalutamide demonstrated clinical activity and was well tolerated in patients with advanced AR-positive TNBC. Adverse events related to enzalutamide were consistent with its known safety profile. This study supports additional development of enzalutamide in advanced TNBC.

Tambur, A. R., P. Campbell, F. H. Claas, S. Feng, H. M. Gebel, A. M. Jackson, R. B. Mannon, E. F. Reed, K. Tinckam, M. Askar, A. Chandraker, P. P. Chang, M. Colvin, A. J. Demetris, J. M. Diamond, A. I. Dipchand, R. L. Fairchild, M. L. Ford, J. Friedewald, R. G. Gill, D. Glotz, H. Goldberg, R. Hachem, S. Knechtle, J. Kobashigawa, D. J. Levine, J. Levitsky, M. Mengel, E. Milford, K. A. Newell, J. G. O’Leary, S. Palmer, P. Randhawa, J. Smith, L. Snyder, R. C. Starling, S. Sweet, T. Taner, C. J. Taylor, S. Woodle, A. Zeevi and P. Nickerson (2018). “Sensitization in Transplantation: Assessment of Risk (STAR) 2017 Working Group Meeting Report.” Am J Transplant Mar 30. [Epub ahead of print].

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The presence of pre-existing (memory) or de novo donor specific HLA antibodies (DSA) is a known barrier to successful long-term organ transplantation. Yet, despite the fact that laboratory tools and our understanding of histocompatibility have advanced significantly in recent years, the criteria to define presence of a DSA and assign a level of risk for a given DSA varies markedly between centers. A collaborative effort between ASHI and the AST provided the logistical support for generating a dedicated multidisciplinary working group, which included experts in histocompatibility as well as renal, liver, heart and lung transplantation. The goal was to perform a critical review of biologically driven, state-of-the-art, clinical diagnostics literature; and to provide clinical practice recommendations based on expert assessment of quality and strength of evidence. The results of the STAR (Sensitization in Transplantation: Assessment of Risk) meeting are summarized here, providing recommendations on the definition and utilization of HLA diagnostic testing, and a framework for clinical assessment of risk for a memory or a primary alloimmune response. The definitions, recommendations, risk framework, as well as highlighted gaps in knowledge are intended to spur research that will inform the next STAR working group meeting in 2019. This article is protected by copyright. All rights reserved.

Stewart, R. J., B. Flannery, J. R. Chung, M. Gaglani, M. Reis, R. K. Zimmerman, M. P. Nowalk, L. Jackson, M. L. Jackson, A. S. Monto, E. T. Martin, E. A. Belongia, H. Q. McLean, A. M. Fry and F. P. Havers (2018). “Influenza Antiviral Prescribing for Outpatients With an Acute Respiratory Illness and at High Risk for Influenza-Associated Complications During 5 Influenza Seasons-United States, 2011-2016.” Clin Infect Dis 66(7): 1035-1041.

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Background: Influenza causes millions of illnesses annually; certain groups are at higher risk for complications. Early antiviral treatment can reduce the risk of complications and is recommended for outpatients at increased risk. We describe antiviral prescribing among high-risk outpatients for 5 influenza seasons and explore factors that may influence prescribing. Methods: We analyzed antiviral prescription and clinical data for high-risk outpatients aged >/=6 months with an acute respiratory illness (ARI) and enrolled in the US Influenza Vaccine Effectiveness Network during the 2011-2012 through 2015-2016 influenza seasons. We obtained clinical information from interviews and electronic medical records and tested all enrollees for influenza with real-time reverse-transcription polymerase chain reaction (rRT-PCR). We calculated the number of patients with ARI that must be treated to treat 1 patient with influenza. Results: Among high-risk outpatients with ARI who presented to care within 2 days of symptom onset (early), 15% (718/4861) were prescribed an antiviral medication, including 472 of 1292 (37%) of those with rRT-PCR-confirmed influenza. Forty percent of high-risk outpatients with influenza presented to care early. Earlier presentation was associated with antiviral treatment (odds ratio [OR], 4.1; 95% confidence interval [CI], 3.5-4.8), as was fever (OR, 3.2; 95% CI, 2.7-3.8), although 25% of high-risk outpatients with influenza were afebrile. Empiric treatment of 4 high-risk outpatients with ARI was needed to treat 1 patient with influenza. Conclusions: Influenza antiviral medications were infrequently prescribed for high-risk outpatients with ARI who would benefit most. Efforts to increase appropriate antiviral prescribing are needed to reduce influenza-associated complications.

Spechler, S. J., D. A. Katzka and R. C. Fitzgerald (2018). “New Screening Techniques in Barrett’s Esophagus: Great Ideas or Great Practice?” Gastroenterology Mar 23. [Epub ahead of print].

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Recommendations: We support the current recommendation of GI societies that screening endoscopy for Barrett’s esophagus should be performed only in a well-defined, high-risk population. We do not recommend the use of any alternative test to screen for Barrett’s esophagus at this time. Some of the alternative tests show great promise for Barrett’s screening and will likely find a place in clinical practice in the near future. In addition to refinement and validation of the alternative tests, there should be a complementary focus on using readily available demographic and clinical factors as well as noninvasive tools to further define an acceptable screening population for the next step in screening procedures. The stringency with which these populations can be defined will need to be balanced with the costs and risks of the potential screening tools proposed. (Excerpt from text, p. 6; no abstract available.)

Souza, R. F., J. H. Rubenstein, J. Y. Kao and I. Hirano (2018). “Contributions From Gastroenterology: Acid Peptic Disorders, Barrett’s Esophagus and Eosinophilic Esophagitis.” Gastroenterology 154(5): 1209-1214.

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Over the past three-quarters of a century, manuscripts published in Gastroenterology have had a substantial impact on our clinical recognition, understanding, and management of peptic ulcer disease (PUD), Helicobacter pylori, gastroesophageal reflux disease (GERD), Barrett’s esophagus, and eosinophilic esophagitis (EoE). This article highlights selected, highly cited works with overlapping themes of acid injury, chronic mucosal inflammation, and H pylori infection.