{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:28:33Z","timestamp":1792214913959,"version":"4.4.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T00:00:00Z","timestamp":1732320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"G1 Therapeutics, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>In metastatic colorectal cancer (mCRC), improvements in survival from combining leucovorin\/fluorouracil\/oxaliplatin\/irinotecan (FOLFOXIRI) with bevacizumab have come at the risk of increased rates of high-grade toxicities. Trilaciclib is indicated to decrease the incidence of chemotherapy-induced myelosuppression in patients receiving standard-of-care chemotherapy for extensive-stage small cell lung cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Patients with untreated mCRC were randomly assigned 1:1 to trilaciclib (n\u2009=\u2009164) or placebo (n\u2009=\u2009162) prior to FOLFOXIRI\/bevacizumab for up to 12 cycles (induction), followed by trilaciclib or placebo prior to fluorouracil\/leucovorin\/bevacizumab (maintenance). Co-primary endpoints were duration of severe (grade 4) neutropenia (DSN) in cycles 1-4 and occurrence of severe neutropenia (SN) during induction. Secondary endpoints included antitumor efficacy, survival, and safety.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The study met its co-primary endpoints. Administering trilaciclib prior to FOLFOXIRI\/bevacizumab resulted in significant reductions in DSN in cycles 1-4 vs placebo (mean, 0.1 vs 1.3\u2009days; P\u2009&amp;lt;\u2009.001) and occurrence of SN during induction (1.3% vs 19.7%; adjusted relative risk [96% CI] = 0.07 [0.0 to 0.3]; P\u2009&amp;lt;\u2009.001). Grade 3\/4 adverse events, including neutropenia, diarrhea, and leukopenia, were less frequent with trilaciclib vs placebo (64.8% vs 73.1%). Trilaciclib was associated with fewer chemotherapy dose reductions and delays and with reduced administration of supportive therapies, compared with placebo. Objective response rate (41.6% vs 57.1%; P\u2009=\u2009.009) and median progression-free survival (10.3 vs 13.1\u2009months; P\u2009&amp;lt;\u2009.001) were significantly lower with trilaciclib vs placebo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Administering trilaciclib prior to FOLFOXIRI\/bevacizumab protected the neutrophil lineage from the effects of chemotherapy-induced myelosuppression. However, antitumor efficacy endpoints favored placebo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration<\/jats:title>\n                  <jats:p>ClinicalTrials.gov: NCT04607668.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jncics\/pkae116","type":"journal-article","created":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T14:33:06Z","timestamp":1732372386000},"source":"Crossref","is-referenced-by-count":10,"title":["Trilaciclib prior to FOLFOXIRI\/bevacizumab for patients with untreated metastatic colorectal cancer: phase 3 PRESERVE 1 trial"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2178-9568","authenticated-orcid":false,"given":"Heinz-Josef","family":"Lenz","sequence":"first","affiliation":[{"name":"Department of Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center , Los Angeles, CA 90033,","place":["United 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