{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:24:30Z","timestamp":1792783470911,"version":"4.5.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"HUTCHMED","id":[{"id":"https:\/\/ror.org\/00wnvbd12","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Clin Oncol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In the phase 3 FRESCO-2 study, fruquintinib plus best supportive care (BSC) significantly improved overall survival (OS) versus placebo plus BSC in patients with refractory metastatic colorectal cancer (mCRC). We present the results of a FRESCO-2 post hoc subgroup analysis evaluating outcomes of patients enrolled in Japan.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In FRESCO-2, patients had previously received all standard chemotherapies, anti-VEGF and anti-EGFR therapies if indicated, and had progressed on, or were intolerant to trifluridine-tipiracil and\/or regorafenib. Patients were randomized 2:1 to receive fruquintinib 5\u00a0mg or matching placebo by mouth once daily on days 1\u201321 in 28-day cycles, plus BSC. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS) and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 56 patients enrolled in Japan, 40 (71.4%) and 16 (28.6%) were randomized to fruquintinib and placebo, respectively. OS was improved with fruquintinib versus placebo (median 6.9 vs. 5.6\u00a0months; hazard ratio [HR], 0.42; 95% confidence interval [CI] 0.19\u2009\u2212\u20090.92). PFS was also improved with fruquintinib versus placebo (median 3.6 vs. 1.8\u00a0months; HR, 0.27; 95% CI 0.13\u2009\u2212\u20090.56). The incidence of grade\u2009\u2265\u20093 treatment-emergent adverse events (TEAEs) with fruquintinib versus placebo was 71.8% versus 29.4%; the most common grade\u2009\u2265\u20093 TEAEs with fruquintinib were hypertension (23.1%) and palmar-plantar erythrodysesthesia (17.9%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Fruquintinib improved OS and PFS versus placebo in FRESCO-2 patients enrolled in Japan and demonstrated a manageable safety profile. Results from the Japan subgroup were consistent with the global FRESCO-2 population, thus supporting fruquintinib as a novel treatment option for patients in Japan with refractory mCRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial details<\/jats:title>\n                    <jats:p>ClinicalTrials.gov; NCT04322539.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10147-025-02852-9","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T11:41:29Z","timestamp":1756726889000},"page":"2043-2052","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer: a FRESCO-2 subgroup analysis of patients enrolled in Japan"],"prefix":"10.1007","volume":"30","author":[{"given":"Daisuke","family":"Kotani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Yoshino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Masuishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Sunakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuo","family":"Takashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisato","family":"Kawakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Nishina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshito","family":"Komatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taito","family":"Esaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy","family":"Eng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey","family":"Ukrainskyj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajash","family":"Pallai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivani","family":"Nanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Schelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Kania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taroh","family":"Satoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"2852_CR1","unstructured":"Foundation for Promotion of Cancer Research (2024) Cancer statistics in Japan. https:\/\/ganjoho.jp\/public\/qa_links\/report\/statistics\/pdf\/cancer_statistics_2024_fig_E.pdf. 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and reports grants or funds from Ono Pharmaceutical, MSD, Novartis, Servier, Janssen, IQVIA, Syneos Health, CIMIC, and CMIC Shift Zero.\n                      TY\n                      has received honoraria from Chugai, Takeda, Merck Biopharma, Bayer Yakuhin, Ono Pharmaceutical, and MSD; consulting fees from Sumitomo Corp; and reports grants or funds from Amgen, Bristol Myers Squibb, Chugai, Daiichi\u00a0Sankyo, Eisai, FALCO Biosystems, Genomedia, Medical & Biological Laboratories, Merus N.V., Molecular Health GmbH, MSD, Nippon Boehringer Ingelheim, Ono Pharmaceutical, Pfizer Japan, Roche Diagnostics, Sanofi, Sysmex, Taiho, and Takeda.\n                      TM\n                      has received honoraria from Bayer Yakuhin, Bristol Myers Squibb, Chugai, Daiichi\u00a0Sankyo, Eli Lilly, Merck Serono, Ono Pharmaceutical, Sanofi, Taiho, Takeda, Yakult Honsha, MSD, Takata, Astellas, and Nippon Kayaku; and reports grants or funds from Amgen, Boehringer Ingelheim, CMIC, Daiichi\u00a0Sankyo, Eli Lilly Japan, MSD, Novartis, Ono Pharmaceutical, Pfizer, and Syneos Health.\n                      YS\n                      has received honoraria and grants or funds from Takeda.\n                      KY\n                      reports honoraria from Chugai, Daiichi\u00a0Sankyo, Yakult Honsha, Takeda, Merck Serono, Taiho, Eli Lilly, Ono Pharmaceutical, MSD, and Bristol Myers Squibb; and grants or funds from Taiho.\n                      HK\n                      reports honoraria from Bristol Myers Squibb, Bayer Yakuhin, Eli Lilly Japan K.K., MSD, Ono Pharmaceutical, Chugai, Daiichi\u00a0Sankyo, Merck Biopharma, Takeda, Yakult Pharmaceutical Industry, Teijin Pharma, Taiho, Otsuka Pharmaceutical, Nippon Kayaku, GlaxoSmithKline, Amgen, Novartis, and Astellas; consulting fees from Daiichi\u00a0Sankyo, Astellas, and AbbVie; grants or funds from Eisai, Bristol Myers Squibb, Kobayashi Pharmaceutical, Astellas, Taiho; and other potential financial relationship with Medical & Biological Laboratories.\n                      TN\n                      reports honoraria from Astellas, and Ono Pharmaceutical.\n                      YK\n                      has received honoraria from Ono Pharmaceutical, Taiho, Chugai, Eli Lilly, Bayer, MSD, Astellas, Yakult, Daiichi\u00a0Sankyo, and Incyte; and reports grants or funds from Ono Pharmaceutical, Taiho, Chugai, Eli Lilly, Bayer, MSD, Astellas, Yakult, Daiichi\u00a0Sankyo, Incyte, Eisai, NCCH, Syneos Health, CMIC, and Parexel.\n                      TE\n                      has received honoraria from Chugai, Taiho, Ono Pharmaceutical, Hisamitsu, Roche Diagnostics, Zeria, MSD, Eli Lilly, and Daiichi\u00a0Sankyo; and grants or funds from Ono Pharmaceutical, Seagen, Taiho, Jazz Pharmaceuticals, Ignyta, Quintiles, Bristol Myers Squibb, Asahi Kasei Pharma, ALX Oncology, MSD, Nihon Kayaku, Astellas, Amgen, IQVIA, Daiichi\u00a0Sankyo, Chugai, Syneos Health Clinical, Pfizer, and Amgen.\n                      CE\n                      reports consulting fees from Amgen, Elevation, GlaxoSmithKline, GE\u00a0HealthCare, IGM, Merck Biopharma, Natera, Pfizer, Seagen, Taiho, AbbVie, and Takeda; and potential financial relationships paid to Vanderbilt from Janssen, Merck Biopharma, Gritstone, and Hutchinson.\n                      SN\n                      is employed by and holds stocks\/shares with HUTCHMED International Corporation.\n                      WS\n                      is an employee of and holds stocks\/shares with HUTCHMED International Corporation.\n                      MK\n                      was a previous HUTCHMED International Corporation employee during study conduct and analysis.\n                      TS\n                      has received honoraria from MSD, AstraZeneca, Ono Pharmaceutical, Bristol Myers Squibb, and Daiichi\u00a0Sankyo; and reports grants or funds from MSD, AstraZeneca, Ono Pharmaceutical, Bristol Myers Squib, Daiichi\u00a0Sankyo, Shionogi Pharmaceutical, and Janssen.\n                      AT\n                      ,\n                      SU\n                      ,\n                      RP\n                      , and\n                      ZY\n                      have no conflicts to report.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"FRESCO-2 was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines, including the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, and all applicable laws and regulations. The protocol was approved by the institutional review boards and independent ethics committees at each site. All participating patients provided written informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}