Abstract
Introduction Chemotherapy-induced myelosuppression (CIM) is among the most clinically significant hematologic toxicities associated with cytotoxic chemotherapy, leading to neutropenia, anemia, thrombocytopenia, and an increased risk of infections. Despite the routine use of G-CSF, erythropoiesis-stimulating agents (ESAs), and transfusions, CIM remains a frequent and inadequately managed complication, often resulting in chemotherapy delays, hospitalizations, and reduced treatment intensity. Trilaciclib is a short-acting CDK4/6 inhibitor that offers a proactive approach by transiently inducing G1 cell cycle arrest in hematopoietic stem and progenitor cells (HSPCs), thereby potentially protecting them against chemotherapy-induced damage. We aimed to evaluate efficacy and safety of Trilaciclib in preventing CIM in the treatment of advanced cancers.
Methods We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating Trilaciclib administered prior to chemotherapy in adult patients (≥18 years) with advanced or metastatic solid tumors. Databases searched included PubMed, Embase, the Cochrane Library, and major trial registries (ClinicalTrials.gov, EU Clinical Trials Register, ICTRP) up to May 21, 2025. Primary outcomes were incidence of grade 3/4 neutropenia, febrile neutropenia (FN), need for granulocyte-colony stimulating factors/erythropoiesis stimulating agents, and need for red blood cell/platelet transfusions, and efficacy endpoints included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Secondary outcomes were adverse events associated with the use of Trilaciclib. Pooled odds ratios (OR) or hazard ratios (HR) were calculated using a random-effects model. Heterogeneity was assessed with the I² statistic. Sensitivity and subgroup analyses were conducted to explore robustness of results and sources of heterogeneity.
Results Ten studies with a total of 979 patients were included, with 586 receiving Trilaciclib (240 mg/m2) prior to chemotherapy and 393 receiving chemotherapy alone. Six of the 10 included studies pertained to extensive-stage small cell lung cancer (ES-SCLC), two to triple negative breast cancer, and one to non-small cell lung cancer and colorectal cancer each. Chemotherapy regimens were heterogeneous and included etoposide-platinum (E/P) (either cisplatin or carboplatin) (n=5), gemcitabine/carboplatin (GCb) (n=2), topotecan (n=2), FOLFOXIRI (n=1), and Carboplatin/Paclitaxel/Tislelizumab (n=1). Pooled analysis showed that Trilaciclib decreased the incidence of grade 3/4 neutropenia by 79% (OR = 0.21; 95% CI: 0.08–0.52; I² = 71%), febrile neutropenia (FN) by 75% (OR = 0.25; 95% CI: 0.14–0.46; I² = 0%), grade 3/4 anemia by 60% (OR = 0.40; 95% CI: 0.28–0.57; I² = 0%) and ESA use by 56% (OR = 0.44; 95% CI: 0.26–0.77; I² = 0%). Duration of severe neutropenia (DSN) was shorter in patients receiving Trilaciclib (Mean Difference = −1.92 days; 95% CI: −3.80 to −0.04; I² = 91%). Sensitivity analysis markedly reduced heterogeneity in outcomes and demonstrated a statistically significant decrease in mortality (OR = 0.23; 95% CI: 0.10–0.54; I² = 0%). Significant improvements were also observed in PFS (HR = 0.77; 95% CI: 0.66–0.90; I² = 0%) and OS (HR = 0.58; 95% CI: 0.36–0.94; I² = 72%). Adverse events such as nausea, fatigue, vomiting, diarrhea, and ≥grade 3 AEs were comparable between both arms, demonstrating a favorable safety profile as well.
Conclusion Trilaciclib demonstrated clear benefit in reducing the incidence of chemotherapy-induced myelosuppression and the need for hematopoietic support. It also showed a positive impact on progression-free and overall survival, without compromising chemotherapy effectiveness or increasing toxicity. These findings highlight Trilaciclib's potential as a valuable adjunct to chemotherapy in appropriately selected patients.
