{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:12:11Z","timestamp":1791994331677,"version":"4.4.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Takeda Pharmaceuticals America, Inc., Cambridge, MA, USA"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Guideline-recommended nontargeted systemic therapies for previously treated metastatic colorectal cancer (mCRC) include regorafenib, trifluridine\/tipiracil, and fruquintinib, but no consensus exists on the definition of clinically meaningful improvements for later-line mCRC treatments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Trials were identified from systematic searches in MEDLINE, Embase, and the Cochrane Library. Meta-analyses were performed to characterize overall survival (OS) and progression-free survival (PFS) improvements with systemic therapy vs placebo in previously treated mCRC. Meta-analyses were conducted using fixed-effect and random-effects (RE) frequentist models of difference in medians, hazard ratios (HRs), and 12-month restricted mean survival time (RMST).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Six randomized, placebo-controlled, phase III trials of 3277 patients comparing oral systemic monotherapies with placebo were analyzed. Using the RE model, the meta-analyzed OS estimate for oral systemic monotherapy vs placebo was 1.86\u2009months (95% confidence interval [CI], 1.30-2.42) for the difference in medians, 0.69 (95% CI, 0.64-0.76) for HRs, and 1.25\u2009months (95% CI, 0.69-1.82) for the difference in 12-month RMST. For PFS, meta-analyzed median improvement was 0.97\u2009months (95% CI, 0.28-1.66), HR was 0.38 (95% CI, 0.30-0.47), and 12-month RMST difference was 1.90\u2009months (95% CI, 1.41-2.39). Sensitivity analyses, excluding the FRESCO-2 trial due to prior treatment differences, confirmed the primary meta-analysis results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>When assessing the clinical benefit of later-line mCRC treatments, the broad clinical picture, including individualized treatment goals, should be evaluated. Considering multiple survival measures in the later-line mCRC context, an incremental survival improvement with oral systemic monotherapy vs no active therapy is clinically meaningful.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag175","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T11:39:57Z","timestamp":1778067597000},"source":"Crossref","is-referenced-by-count":1,"title":["Survival benefit of oral systemic monotherapy in previously treated metastatic colorectal cancer: a meta-analysis"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2925-0586","authenticated-orcid":false,"given":"Per","family":"Pfeiffer","sequence":"first","affiliation":[{"name":"Department of Oncology, Odense University Hospital , 5000 Odense,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0520-4841","authenticated-orcid":false,"given":"Chiara","family":"Cremolini","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa , 56126 Pisa,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8649-7449","authenticated-orcid":false,"given":"Michel","family":"Ducreux","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Paris-Saclay University, Gustave Roussy and INSERM-U1279, Collective Invasion , 94800 Villejuif,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7124-3515","authenticated-orcid":false,"given":"Pia","family":"Osterlund","sequence":"additional","affiliation":[{"name":"Department of Oncology, Tampere University Hospital Comprehensive Cancer Center and University of Tampere , 33100 Tampere,","place":["Finland"]},{"name":"Department of Oncology, Tema Cancer\/GI-Cancer, Karolinska University Hospital, Comprehensive Cancer Center , SE-171 76 Solna,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4787-754X","authenticated-orcid":false,"given":"Sarah","family":"Ronnebaum","sequence":"additional","affiliation":[{"name":"PPD Evidera Health Economics and Market Access, Thermo Fisher Scientific , Wilmington, NC 28401,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morodoluwa","family":"Akin-Fajiye","sequence":"additional","affiliation":[{"name":"PPD Evidera Health Economics and Market Access, Thermo Fisher Scientific , Wilmington, NC 28401,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Paly","sequence":"additional","affiliation":[{"name":"Global Pricing, Value & Access; 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