The phase 3 PRESERVE 1 trial has revealed significant myeloprotective benefits of trilaciclib when administered prior to FOLFOXIRI and bevacizumab in patients with untreated metastatic colorectal cancer (CRC), while simultaneously raising questions about its impact on treatment efficacy.
Significant Myeloprotection Benefits
The multicenter study, conducted across 88 sites in 8 countries, demonstrated remarkable protection against chemotherapy-induced myelosuppression. Patients receiving trilaciclib experienced a mean duration of severe neutropenia of just 0.1 days compared to 1.3 days in the placebo group during the first four treatment cycles (P <.001). The incidence of severe neutropenia was dramatically reduced to 1.3% in the trilaciclib arm versus 19.7% in the placebo group.
Notably, trilaciclib completely prevented febrile neutropenia, with zero cases reported compared to 5% in the placebo group. The need for granulocyte colony-stimulating factor (G-CSF) support was also significantly reduced, with only 19.5% of trilaciclib patients requiring G-CSF compared to 43.5% in the placebo arm (P <.001).
Treatment Protocol and Patient Demographics
The trial enrolled 296 patients aged 18 and older with confirmed proficient mismatch repair/microsatellite stable (pMMR/MSS) unresectable metastatic CRC. Patients were randomized 1:1 to receive either trilaciclib or placebo before FOLFOXIRI/bevacizumab treatment. The median age was 58 years in the trilaciclib arm and 55 years in the placebo arm, with male patients comprising approximately 62% of both groups.
Efficacy Outcomes and Safety Profile
Despite the strong myeloprotection results, the efficacy data presented some concerns. The confirmed objective response rate was lower in the trilaciclib arm at 41.6% compared to 57.1% in the placebo group. Disease control rates were comparable between the arms at 90.5% and 92.9%, respectively.
The safety profile showed encouraging results, with grade 3/4 adverse events occurring in 64.8% of trilaciclib patients versus 73.1% in the placebo group. Common adverse events included diarrhea (63.0%), nausea (58.6%), and neutropenia (48.0%).
Expert Perspective
Dr. Heinz-Josef Lenz, professor at the Keck School of Medicine of USC, noted the study's mixed results: "While trilaciclib effectively protected against chemotherapy-induced myelosuppression, early survival indicators did not favor trilaciclib over placebo." This observation suggests the need for careful consideration in determining optimal treatment strategies for metastatic CRC patients.
