Trilaciclib prior to FOLFOXIRI/bevacizumab for patients with untreated metastatic colorectal cancer: phase 3 PRESERVE 1 trial

Lenz, Heinz-Josef, Liu, Tianshu, Chen, Emerson Y, Horváth, Zsolt, Bondarenko, Igor, Danielewicz, Iwona, Ghidini, Michele, García-Alfonso, Pilar, Jones, Robert ORCID: https://orcid.org/0000-0003-3576-9496, Aapro, Matti, Zhang, Yanqiao, Wang, Jufeng, Wang, Wayne, Adeleye, Jennifer, Beelen, Andrew and Hubbard, Joleen 2024. Trilaciclib prior to FOLFOXIRI/bevacizumab for patients with untreated metastatic colorectal cancer: phase 3 PRESERVE 1 trial. JNCI Cancer Spectrum , pkae116. 10.1093/jncics/pkae116

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Abstract

Background: 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. Methods: Patients with untreated mCRC were randomized 1:1 to trilaciclib (n = 164) or placebo (n = 162) 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. Results: The study met its co-primary endpoints. Administering trilaciclib prior to FOLFOXIRI/bevacizumab resulted in significant reductions in DSN in cycles 1-4 versus placebo (mean, 0.1 vs. 1.3 days; P < .001) and occurrence of SN during induction (1.3% vs. 19.7%; adjusted relative risk [96% CI], 0.07 [0.0, 0.3]; P < .001). Grade 3/4 adverse events, including neutropenia, diarrhea, and leukopenia, were less frequent with trilaciclib versus placebo (64.8% vs. 73.1%). Trilaciclib was associated with fewer chemotherapy dose reductions and delays, and reduced administration of supportive therapies, compared with placebo. Objective response rate (41.6% vs. 57.1%; P = .009) and median progression-free survival (10.3 vs. 13.1 months; P < .001) were significantly lower with trilaciclib versus placebo. Conclusions: Administering trilaciclib prior to FOLFOXIRI/bevacizumab protected the neutrophil lineage from the effects of chemotherapy-induced myelosuppression. However, antitumor efficacy endpoints favored placebo.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Medicine
Publisher:	Oxford University Press
ISSN:	2515-5091
Date of First Compliant Deposit:	28 November 2024
Date of Acceptance:	13 November 2024
Last Modified:	28 Nov 2024 14:45
URI:	https://orca.cardiff.ac.uk/id/eprint/174322

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