{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T08:15:10Z","timestamp":1765440910814,"version":"3.46.0"},"reference-count":4,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100032128","name":"Taiho Oncology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100032128","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ramucirumab plus paclitaxel after progression on fluoropyrimidine\/platinum in metastatic gastric (GA) and gastroesophageal junction adenocarcinoma (GEJC) has shown improvement in overall survival over paclitaxel alone. However, the incidence of neuropathy was 46%. Therefore, there is an unmet need for novel treatment to minimize the long-term toxicity of neuropathy. We conducted a single arm phase II study of ramucirumab and trifluridine\/tipiracil (FTD\/TPI) in metastatic GA\/GEJC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients received ramucirumab at 8\u2009mg\/kg intravenously on day 1 and 15, and FTD\/TPI at 35\u2009mg\/m2 orally twice daily on days 1-5 and days 8-12 on every 28-days cycle. The primary endpoint was 6-months overall survival (OS) rate and secondary endpoints were progression free survival (PFS), objective response rate and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At data cut-off of August 15, 2021, 23 pts were enrolled. The median age was 62\u2009years. Most common treatment-related toxicities were diarrhea (39%), fatigue (39%), hypertension (39%), and nausea (35%). Most common treatment related Grade 3 or 4 adverse events were neutropenia (17%) and anemia (13%). The median PFS and OS was 4.8 and 6.1\u2009months, respectively. The 6-month OS rate was 57% (95% CI: 36.4%-79.8%). Of the 18 evaluable patients with at least one post-baseline imaging, 2 (11%) patients demonstrated objective partial response, and 15 (83%) had stable disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The combination of ramucirumab and FTD\/TPI demonstrated well-manageable safety profile. Our study did not meet primary endpoint. Ongoing clinical trials will help us understand if ramucirumab plus FTD\/TPI is noninferior to ramucirumab\/paclitaxel. The trial was registered at www.clinicaltrials.gov (NCT03686488).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyaf303","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T13:18:39Z","timestamp":1764767919000},"source":"Crossref","is-referenced-by-count":0,"title":["A phase II study of trifluridine\/tipiracil in combination with ramucirumab in advanced, refractory gastric, or gastroesophageal junction adenocarcinomas"],"prefix":"10.1093","volume":"30","author":[{"given":"Dae Won","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Oncology, Moffitt Cancer Center , Tampa, FL 33647,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard D","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology, Moffitt Cancer Center , Tampa, FL 33647,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Martinez","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Oncology, Moffitt Cancer Center , Tampa, FL 33647,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youngchul","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Moffitt Cancer Center , Tampa, FL,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4277-0153","authenticated-orcid":false,"given":"Rutika","family":"Mehta","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, Weill Cornell Medicine\/New York Presbyterian Hospital , New York, NY,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"2025121103120812900_oyaf303-B1","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1002\/ijc.34652","article-title":"Ramucirumab beyond progression plus TAS-102 in patients with advanced or metastatic esophagogastric adenocarcinoma, after treatment failure on a ramucirumab-based therapy","volume":"153","author":"Goetze","year":"2023","journal-title":"Int J Cancer"},{"key":"2025121103120812900_oyaf303-B2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S2468-1253(20)30396-4","article-title":"Safety and activity of trifluridine\/tipiracil and ramucirumab in previously treated advanced gastric cancer: an open-label, single-arm, phase 2 trial","volume":"6","author":"Kawazoe","year":"2021","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2025121103120812900_oyaf303-B3","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1200\/JCO.2022.40.4_suppl.284","article-title":"Ramucirumab and irinotecan in patients with previously treated gastroesophageal adenocarcinoma: final analysis of a phase II trial","volume":"40","author":"Park","year":"2022","journal-title":"J Clin Oncol"},{"key":"2025121103120812900_oyaf303-B4","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ejca.2022.01.015","article-title":"FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for patients with advanced or metastatic gastroesophageal adenocarcinoma with or without prior docetaxel\u2014results from the phase. RAMIRIS study of the german gastric cancer study group at AIO","volume":"165","author":"Lorenzen","year":"2022","journal-title":"Eur J Cancer"}],"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article-pdf\/doi\/10.1093\/oncolo\/oyaf303\/65728432\/oyaf303.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/30\/12\/oyaf303\/65728432\/oyaf303.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/article-pdf\/30\/12\/oyaf303\/65728432\/oyaf303.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T08:12:14Z","timestamp":1765440734000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/article\/doi\/10.1093\/oncolo\/oyaf303\/8363890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,1]]},"references-count":4,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12,1]]}},"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyaf303","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"type":"print","value":"1083-7159"},{"type":"electronic","value":"1549-490X"}],"subject":[],"published-other":{"date-parts":[[2025,12]]},"published":{"date-parts":[[2025,12,1]]},"article-number":"oyaf303"}}