A prospective, single-arm phase II study of trilaciclib combined with immunotherapy and chemotherapy as first-line treatment for metastatic/recurrent esophageal squamous cell carcinoma.

Abstract

411 Background: Immunotherapy combined with chemotherapy has become the first-line treatment for advanced esophageal squamous cell carcinoma (ESCC) , but myelosuppression remains a common Adverse Event. However, existing preventive measures have limitations, and there is a lack of multi-lineage prevention and treatment strategies. Trilaciclib is a highly effective, selective, and transiently reversible cyclin-dependent kinase 4/6 inhibitor. Administered intravenously prior to chemotherapy, it protects hematopoietic stem and progenitor cells, thereby reducing chemotherapy-induced myelosuppression. We conducted this study to evaluate the efficacy and safety of trilaciclib in patients with advanced ESCC receiving immunotherapy combined with chemotherapy. Methods: Patients with unresectable metastatic/recurrent ESCC received trilaciclib (240 mg/m², IV, Q3W) combined with immunotherapy (Q3W), paclitaxel (175 mg/m², IV, Q3W), and carboplatin (AUC = 4-6, IV, Q3W). Chemotherapy was administered for ≤ 6 cycles. Trilaciclib was administered for the same number of cycles as chemotherapy. Each treatment cycle was 21 days, and treatment continued until disease progression, intolerable toxicity, completion of the protocol-specified treatment duration, or patient withdrawal. The primary endpoint was the incidence of grade ≥ 3 neutropenia during chemotherapy. Secondary endpoints included the incidence of grade ≥ 3 thrombocytopenia during chemotherapy, incidence of grade ≥ 3 anemia during chemotherapy, disease control rate (DCR), progression-free survival (PFS), and safety (adverse events [AEs]). Results: As of April 23, 2025, 10 patients were enrolled, with a median age of 65.5 years. For 90% of pts, an ECOG performance status (PS) of 0 was documented at baseline assessment (10% ECOG PS 1). During chemotherapy, 10 patients (100%) developed neutropenia, 1 patient (10%) developed anemia, and no patient developed thrombocytopenia. Among these, only 1 patient (10%) had grade ≥ 3 neutropenia, and no grade ≥ 3 anemia or thrombocytopenia was observed. Other AEs were mainly grade 1-2, including decreased appetite (50%), fatigue (40%), headache (40%), and alopecia (10%). Nine patients (90%) had stable disease (SD), resulting in a DCR of 90%. The median PFS did not reach. Conclusions: The combination of trilaciclib reduced the incidence of grade ≥ 3 chemotherapy-induced myelosuppression in patients with advanced ESCC receiving immunotherapy combined with chemotherapy. Notably, no thrombocytopenia of any grade was observed in this study to date, and no adverse impact on antitumor efficacy was noted. Preliminary results suggest that trilaciclib can improve chemotherapy tolerance in advanced ESCC patients, and further study data are highly anticipated.