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      Efficacy and Safety of Pembrolizumab for Heavily Pretreated Patients With Advanced, Metastatic Adenocarcinoma or Squamous Cell Carcinoma of the Esophagus : The Phase 2 KEYNOTE-180 Study

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          Abstract

          Effective treatment options are limited for patients with advanced, metastatic esophageal cancer progressing after 2 or more lines of systemic therapy.

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          Most cited references16

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          World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.

          (2013)
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            Global cancer statistics, 2012.

            Lindsey A Torre, Freddie Bray, Rebecca Siegel … (2015)
            Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests. © 2015 American Cancer Society.
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              Cancer statistics, 2018

              Kimberly D Miller, Rebecca Siegel, Ahmedin Jemal (2018)
              Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2014, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2015, were collected by the National Center for Health Statistics. In 2018, 1,735,350 new cancer cases and 609,640 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2005-2014) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2006-2015) declined by about 1.5% annually in both men and women. The combined cancer death rate dropped continuously from 1991 to 2015 by a total of 26%, translating to approximately 2,378,600 fewer cancer deaths than would have been expected if death rates had remained at their peak. Of the 10 leading causes of death, only cancer declined from 2014 to 2015. In 2015, the cancer death rate was 14% higher in non-Hispanic blacks (NHBs) than non-Hispanic whites (NHWs) overall (death rate ratio [DRR], 1.14; 95% confidence interval [95% CI], 1.13-1.15), but the racial disparity was much larger for individuals aged <65 years (DRR, 1.31; 95% CI, 1.29-1.32) compared with those aged ≥65 years (DRR, 1.07; 95% CI, 1.06-1.09) and varied substantially by state. For example, the cancer death rate was lower in NHBs than NHWs in Massachusetts for all ages and in New York for individuals aged ≥65 years, whereas for those aged <65 years, it was 3 times higher in NHBs in the District of Columbia (DRR, 2.89; 95% CI, 2.16-3.91) and about 50% higher in Wisconsin (DRR, 1.78; 95% CI, 1.56-2.02), Kansas (DRR, 1.51; 95% CI, 1.25-1.81), Louisiana (DRR, 1.49; 95% CI, 1.38-1.60), Illinois (DRR, 1.48; 95% CI, 1.39-1.57), and California (DRR, 1.45; 95% CI, 1.38-1.54). Larger racial inequalities in young and middle-aged adults probably partly reflect less access to high-quality health care. CA Cancer J Clin 2018;68:7-30. © 2018 American Cancer Society.
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                Author and article information

                Journal
                Title: JAMA Oncology
                Abbreviated Title: JAMA Oncol
                Publisher: American Medical Association (AMA)
                ISSN (Print): 2374-2437
                Publication date Created: April 01 2019
                Publication date (Print): April 01 2019
                Volume: 5
                Issue: 4
                Page: 546
                Affiliations
                [1 ]Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York
                [2 ]Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
                [3 ]Department of Oncology, University College London Hospitals National Health Service Foundation Trust, London, United Kingdom
                [4 ]Center for Esophageal and Gastric Cancer, Dana Farber Cancer Institute, Boston, Massachusetts
                [5 ]Department of Medical Oncology, Institut de Cancérologie de l’Ouest, St Herblain, Nantes, France
                [6 ]Department of Adult Medicine, Institut Gustave Roussy, Villejuif, France
                [7 ]Department of Oncology, Hematology, and Hemostaseology, University Cancer Center Leipzig, Leipzig, Germany
                [8 ]Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
                [9 ]Department of Clinical Oncology, Aichi Cancer Center Hospital, Aichi, Japan
                [10 ]Lung Cancer Branch, National Cancer Center, Goyang, South Korea
                [11 ]Department of Medical Oncology, Washington University School of Medicine in St Louis, St Louis, Missouri
                [12 ]Drug Development Program, Sarah Cannon Research Institute, University College, London, United Kingdom
                [13 ]Department of General Cancer, Centre Oscar-Lambret, Lille, France
                [14 ]Department of Medical Oncology and Hematology, Sansum Clinic, Santa Barbara, California
                [15 ]Department of Oncology, Odense University Hospital, Odense, Denmark
                [16 ]Clinical Research, Merck & Co Inc, Kenilworth, New Jersey
                [17 ]Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
                Article
                DOI: 10.1001/jamaoncol.2018.5441
                PMC ID: 6459121
                PubMed ID: 30570649
                SO-VID: ea18f0e8-f1de-4f83-86b5-785b87979d54
                Copyright © © 2019
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