Exact Sciences Comapany Presentation

Generate rock-solid clinical evidence The NEW ENGLAND JOURNAL of MEDICINE ESTABLISHED IN 1812 APRIL 3, 2014 Multitarget Stool DNA Testing for Colorectal-Cancer Screening Thomas F. Imperiale, M.D., David F. Ransohoff, M.D., Steven H. Itzkowitz, M.D., Theodore R. Levin, M.D., Philip Lavin, Ph.D., Graham P. Lidgard, Ph.D., David A. Ahlquist, M.D., and Barry M. Berger, M.D. ABSTRACT BACKGROUND An accurate, noninvasive test could improve the effectiveness of colorectal-cancer From the Department of Medicine, Indi screening. ana University School of Medicine, the Regenstrief Institute, the Simon Cancer Center, and the Center for Innovation at Roudebush Veterans Affairs Medical METHODS Departments of Medicine and Epidemi- We compared a noninvasive, multitarget stool DNA test with a fecal immunochem-Center-all in Indianapolis (T.F.I.); the ical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 meth- ylation, and B-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings. ology and the Lineberger Comprehensive Cancer Center, University of North Caro- lina at Chapel Hill, Chapel Hill (D.F.R.); the Dr. Henry D. Janowitz Division of Gastro- enterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York (S.H.I.): Kaiser Permanente Medical Center, Walnut Creek, CA (T.R.L.); Boston Biostatistics Research Founds- tion, Framingham MA (PL); Exact Sci- ences, Madison, WI (G.PL, B.M.B.); and the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN (D.A.A.). Address reprint requests to Dr. Imperiale at Indiana University Medical Center Regenstrief Institute, 1050 Wis- hard Blvd., Indianapolis, IN 46202 VOL. 370 NO. 14 RESULTS Of the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring 21 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P=0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P=0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT DOI: 10.1056/NEJMoa1311194 were 86.6% and 94.9%, respectively, among participants with nonadvanced or neg-2014 Marche Melical Society ative findings (P<0.001) and 89.8 % and 96.4%, respectively, among those with N Engl J Med 2014;370128797 negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT. EXACT SCIENCES CONCLUSIONS In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results. (Funded by Exact Sciences; ClinicalTrials.gov number, NCT01397747.) This article was published on March 19, 2014, at NEJM.org. The NEW ENGLAND JOURNAL ESTABLISHED IN 1812 of MEDICINE JULY 12, 2018 Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer J.A. Sparano, R.J. Gray, D.F. Makower, K.I. Pritchard, K.S. Albain, D.F. Hayes, C.E. Geyer, Jr., E.C. Dees, M.P. Goetz, J.A. Olson, Jr., T. Lively, S.S. Badve, T.J. Saphner, L.I. Wagner, T.J. Whelan, M.J. Ellis, S. Paik, W.C. Wood, P.M. Ravdin, M.M. Keane, H.L. Gomez Moreno, P.S. Reddy, T.F. Goggins, L.A. Mayer, A.M. Brufsky, D.L. Toppmeyer, V.G. Kaklamani, J.L. Berenberg, J. Abrams, and G.W. Sledge, Jr. ABSTRACT BACKGROUND The recurrence score based on the 21-gene breast cancer assay predicts chemother- apy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score. METHODS We performed a prospective trial involving 10,273 women with hormone-recep tor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer. Of the 9719 eligible patients with follow-up informa- tion, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease-free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death). VOL. 379 NO. 2 RESULTS Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease-free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death (endocrine vs. chemoendocrine therapy), 1.08; 95% con- fidence interval, 0.94 to 1.24; P=0.26). At 9 years, the two treatment groups had similar rates of invasive disease-free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local-regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemotherapy benefit for in- vasive disease-free survival varied with the combination of recurrence score and age (P=0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25. CONCLUSIONS Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger. (Funded by the National Cancer Institute and others; TAILORX ClinicalTrials.gov number, NCT00310180) The authors' full names, academic de- grees, and affiliations are listed in the Ap pendix. Address reprint requests to Dr.. Sparano at Montefiore Medical Center, 1695 Eastchester Rd., Bronx, NY 10461, or at [email protected]. A full list of the investigators in this trial is provided in the Supplementary Appen dix, available at NEJM.org. This article was published on June 3, 2018, at NEJM.org. N Engl J Med 2018,379:111-21. DOI: 10.1056/NEJMoa1804710 Copyright © 2018 M Medical Society Drive profitable revenue Ĉ Invest in world-class talent Provide seamless customer experience 6 New England Journal of Medicine publications 115+ publications and abstracts presented in 2023 Offer tests that impact decision-making 2 Generate rock-solid clinical evidence Increase access & drive adoption 13