Association of trilaciclib use with hematologic outcomes during perioperative immunochemotherapy in resectable esophageal squamous cell carcinoma: a prospective observational cohort study

Background Perioperative immunochemotherapy is a key treatment strategy for resectable esophageal squamous cell carcinoma (ESCC), but chemotherapy-induced myelosuppression (CIM) may compromise treatment delivery. Trilaciclib, a transiently acting, reversible cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, has shown myeloprotective effects in advanced solid tumors; however, evidence in perioperative ESCC is limited. This study investigated the association between trilaciclib use and hematologic outcomes during perioperative immunochemotherapy. Methods In this single-center, prospective observational cohort study, 93 patients (control group, n = 65; trilaciclib group, n = 28) enrolled between October 2023 and March 2026 were analyzed. Stabilized inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Binary, longitudinal, and survival outcomes were analyzed using IPTW-weighted Firth-penalized logistic regression, weighted generalized estimating equations, and weighted Cox models, respectively, with false discovery rate (FDR) adjustment for multiple comparisons. Results After weighting, baseline characteristics were well balanced (all standardized mean differences <0.10). Compared with control, the trilaciclib group had lower weighted incidences of grade 3–4 CIM (3.0% vs. 31.2%; odds ratio [OR] 0.11, 95% confidence interval [CI]: 0.01–0.48; FDR-adjusted P = 0.007), grade 3–4 neutropenia (3.0% vs. 28.3%; OR 0.12, 95% CI: 0.01–0.55; FDR-adjusted P = 0.010), and grade 3–4 anemia (0.0% vs. 17.3%; OR 0.08, 95% CI: <0.01–0.67; FDR-adjusted P = 0.030). Grade 3–4 thrombocytopenia, severe neutropenia, and febrile neutropenia did not differ significantly. Granulocyte colony-stimulating factor (G-CSF) and erythropoiesis-stimulating agent (ESA) use was also lower in the trilaciclib group (34.4% vs. 79.7% and 3.7% vs. 29.6%; FDR-adjusted P < 0.001 and P = 0.010, respectively). Overall survival, disease-free survival, and pathologic outcomes did not differ significantly. These findings should not be interpreted as evidence of equivalence or noninferiority. Conclusion In this small, single-center cohort, trilaciclib use was associated with lower grade 3–4 myelosuppression and less hematopoietic supportive care. No statistically significant unfavorable differences in pathologic or survival outcomes were observed; however, equivalence cannot be inferred. These results are hypothesis-generating and require validation in randomized trials.