Trilaciclib for myeloprotection in adjuvant and first-line chemotherapy for advanced gastric/gastroesophageal junction adenocarcinoma: A multicohort study.

Abstract

12152 Background: Chemotherapy-induced myelosuppression (CIM) has become one of the important limiting factors in the treatment of gastric cancer, which significantly impairs patients' prognosis.Trilaciclib, a highly selective reversible CDK4/6 inhibitor, reduces chemotherapy-induced hematopoietic stem/progenitor cell (HSPC) damage via transient G1 arrest when administered intravenously pre-chemotherapy, while its transient T-cell suppression may modulate the tumor immune microenvironment.This study evaluates trilaciclib’s myeloprotective efficacy in adjuvant and first-line metastatic gastric/gastroesophageal junction adenocarcinoma (GA/GEJA) and explores immunomodulatory effects. Methods: This prospective multicohort study (ChiCTR2500097520) enrolled Cohort 1 (resectable GA/GEJA, T1-4bN0-3M0 post-D2/R0 resection; n = 75) and Cohort 2 (first-line metastatic GA/GEJA, including recurrence > 6 months post-adjuvant; n = 40). Regimens included SOX/XELOX/FOLFOX ± immune checkpoint inhibitors (ICIs) ± trastuzumab. Trilaciclib (240 mg/m²) was given on days 1 and 3 every 21 days for 6–8 cycles. Primary endpoints: incidence of grade ≥3 neutropenia and febrile neutropenia (FN); exploratory analyses included immune biomarkers and antitumor efficacy. Results: As of January 2026, 204 patients were enrolled (male: 158 ; female: 46; median age: 63 years [range: 31–82]). Cohort 1: 118 patients (primary prophylaxis [PP]: 98 ; secondary prophylaxis [SP]: 20 ). Cohort 2: 86 patients (PP: 48 ; SP: 38 ). Grade ≥3 CIM incidence: Cohort 1 vs. Cohort 2: 4.46% vs. 2.96%; grade ≥3 neutropenia: 3.24% vs. 1.73%; thrombocytopenia: 1.54% vs. 0.74%; anemia: 0.77% vs. 1.97%. Prophylaxis-stratified analysis showed superior myeloprotection with PP: overall grade ≥3 CIM (PP:3.35% vs. SP: 4.56%), neutropenia (PP: 2.75% vs. SP:1.83%), thrombocytopenia (PP: 0.6% vs. SP: 2.29%), and anemia (PP: 1.32% vs. SP: 0.91%). Furthermore, the collection and detection of immune cells from 97 patients before and after treatment revealed that: the total number of T cells in patients showed an increasing trend after prophylactic medication. The number of CD4+ T cells showed an increasing trend; the number of CD8+ T cells began to decline after more than 3 cycles of chemotherapy; the number of Treg T cells increased and returned to the pre-chemotherapy level after more than 4 cycles. Conclusions: Trilaciclib demonstrated effective myeloprotection and immunoregulation in GA/GEJA, with PP showing a favorable trend. Grade ≥3 CIM rates were ≤5.88% (adjuvant) and ≤3.49% (metastatic), with no new safety signals. The studies will continue to analyze the correlation between immune-related indicators and anti-tumor efficacy. Clinical trial information: ChiCTR2500097520.