{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:10:43Z","timestamp":1790359843378,"version":"4.1.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T00:00:00Z","timestamp":1559174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Early detection and management of treatment-related adverse events (TRAEs) in patients receiving immune checkpoint inhibitors may improve outcomes. In CheckMate 142, nivolumab (3 mg\/kg) plus low-dose ipilimumab (1 mg\/kg) provided durable clinical benefit (objective response rate [ORR] 55%, median duration of response not reached, 12-month overall survival [OS] rate 85%) and manageable safety for previously treated microsatellite instability-high and\/or mismatch repair-deficient (MSI-H\/dMMR) metastatic colorectal cancer (mCRC). In-depth safety and additional efficacy outcomes from CheckMate 142 are presented.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Safety assessments included frequency of TRAEs, select TRAEs (sTRAEs), and immune-mediated adverse event incidences; time to onset (TTO); time to resolution (TTR); immune-modulating medication (IMM) use; dose delay; and sTRAE occurrence after resuming therapy. Efficacy assessments included ORR and survival analyses in patients with sTRAEs with or without concomitant IMM treatment and patients without sTRAEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 119 patients, 25%, 23%, 19%, 5%, 5%, and 29% experienced an endocrine, gastrointestinal, hepatic, pulmonary, renal, or skin sTRAE, respectively; the majority (57%) were grade 1\/2. sTRAEs occurred early (median TTO, 5.2\u201312.6 weeks). Nonendocrine sTRAEs resolved in most (&amp;gt;71%) patients (median TTR, 1.5\u20139.0 weeks). IMMs were used to manage sTRAEs in 22%\u201356% of patients (most resolved). Of patients with dose delay because of sTRAEs, 25 of 29 resumed treatment. Patients with or without sTRAEs had comparable ORR (57% vs. 52%) and 12-month OS rates (93% vs. 75%). Similar results were observed in patients with or without sTRAEs regardless of IMM use (ORR 52% vs. 57%; OS rates 87% vs. 82%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The benefit-risk profile of nivolumab plus low-dose ipilimumab provides a promising treatment option for patients with previously treated MSI-H\/dMMR mCRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Implications for Practice<\/jats:title>\n                    <jats:p>Nivolumab (NIVO) plus low-dose (1 mg\/kg) ipilimumab (IPI) received U.S. Food and Drug Administration approval for patients with microsatellite instability-high and\/or mismatch repair-deficient (MSI-H\/dMMR) metastatic colorectal cancer (mCRC) that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan based on results from CheckMate 142. In this safety analysis, the majority of select treatment-related adverse events (sTRAEs) occurred early, were managed using evidence-based treatment algorithms, and resolved. Efficacy outcomes were comparable between patients with or without sTRAEs regardless of the use of concomitant immune-modulating medications. The benefit-risk profile of NIVO + low-dose IPI provides a promising treatment option for MSI-H\/dMMR mCRC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1634\/theoncologist.2019-0129","type":"journal-article","created":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T16:39:16Z","timestamp":1559234356000},"page":"1453-1461","source":"Crossref","is-referenced-by-count":101,"title":["Safety of Nivolumab plus Low-Dose Ipilimumab in Previously Treated Microsatellite Instability-High\/Mismatch Repair-Deficient Metastatic Colorectal Cancer"],"prefix":"10.1093","volume":"24","author":[{"given":"Michael A.","family":"Morse","sequence":"first","affiliation":[{"name":"Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Overman","sequence":"additional","affiliation":[{"name":"University of Texas MD Anderson Cancer Center, Houston, Texas, 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