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Editorial Colorectal Cancer Advances in Colorectal and Anal Cancer Treatment Based Upon Selected ASCO 2016 Presentations— Advances in Immunotherapy and Considering the Site of the Primary Tumor in Treatment Decisions Richard M Goldberg The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, US T he colorectal cancer oral session of the ASCO 2016 meeting had two themes: immunotherapy and tumor "sidedness". PD-1 inhibitors were active in patients with anal cancer, with tumors exhibiting microsatellite instability combined with an antibody targeting CTLA-4, and with a Mek inhibitor in microsatellite stable tumors. Three abstracts noted an overall survival advantage for left over right sided colorectal tumors and cetuximab combined with chemotherapy appeared to benefit patients with left but not right sided tumors. Keywords Immunotherapy, PD-1 inhibitors, primary tumor location, colorectal cancer Disclosure: Richard M Goldberg has nothing to disclose in relation to this article. This article is a short opinion piece and has not been submitted to external peer reviewers. No funding was received for the publication of this article. Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: October 17, 2016 Published Online: November 2, 2016 Citation: Oncology & Hematology Review, 2016;12(2):80–1 Corresponding Author: Richard M Goldberg, The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital & Richard J. Solove Research Institute, 320 West Tenth Avenue, B406, US. E: Each June, at the oral sessions of the annual American Society of Clinical Oncology (ASCO) meeting, the ASCO Program Committee’s top ranked abstracts are presented and subjected to expert commentary. These sessions frequently signal the latest directions along which research is evolving and may set new practice standards. At the 2016 meeting, researchers spoke to two dominant themes in the session on colorectal and anal cancer: harnessing immunotherapy for treatment of both colorectal and anal primary tumors and the relevance of the site of the primary colorectal tumor on both prognosis and prediction of treatment responses to targeted therapy. The presentations on immunotherapy promise the potential for future Food and Drug Administration (FDA) approvals for PD-1 inhibitors for indications in gastrointestinal (GI) cancers and they illustrate the need for verification of early results through larger confirmatory trials for combination immunotherapy protocols. The presentations on “tumor sidedness” contain information that is closer to or ready for integration into clinical practice, depending on an individual’s viewpoints. Dr. Cathy Eng from MD Anderson Cancer Center presented data from a multicenter Phase II trial sponsored by Bristol Myers Squibb (BMS) and charitable donations in which patients with advanced, chemotherapy refractory, anal cancer were treated with the programmed death 1 (PD-1) inhibitor, nivolumab. 1 In this study, 37 patients received treatment and 24% had a response while 46% manifested stable disease with a median overall progression free survival (PFS) of 4 months. This is a rare tumor which, when recurrent, has limited chemotherapy options and these tumors are commonly associated with human papilloma virus (HPV) infection. PD-1 inhibitors are active in head and neck cancer which is also HPV associated suggesting broad potential for this approach in virally mediated cancers. 2 The findings suggest the possibility that there will soon be expanded FDA approved options for patients afflicted with this disease. Dr. Michael Overman presented the interim results of a BMS sponsored Phase II study, known as CheckMate 142, using nivolumab (a PD-1 inhibitor) with (in 30 patients) or without (in 70 patients) ipilimumab (an anti-CTLA-4 antibody), with either microsatellite instability high (MSI-H) or MSI stable (MSS) metastatic colorectal (mCRC) tumors. 3 The MSS cohorts had only preliminary results and are not discussed further. The objective response rates (ORR) on nivolumab monotherapy in patients with MSI-H tumors was 25.5% and the stable disease rate was 29.8% with a PFS of 5.3 months. In the combination therapy arm the partial response rate in the patients with MSI-H tumors was 33.3% and 51.9% had stable disease. The median PFS had not yet been reached. Toxicity was tolerable but more severe in the combination therapy cohort as expected. This study confirms the activity of PD-1 inhibition in MSI-H patients and provides preliminary data on the potential for augmented activity with combination immunotherapy. Large studies are needed to better delineate that finding. 80 TOUCH ME D ICA L ME D IA