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

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 randomly assigned 1:1 to trilaciclib (n ¼ 164) or placebo (n ¼ 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 vs 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] ¼ 0.07 [0.0 to 0.3]; P