Trilaciclib prior to chemotherapy in patients with metastatic triple-negative breast cancer: final efficacy and subgroup analysis from a randomized phase II study
Mené sur 102 patientes atteintes d'un cancer du sein triple négatif et de stade métastatique, cet essai de phase II évalue l'efficacité, du point de vue de la survie globale, du trilaciclib (un inhibiteur de CDK 4/6) dispensé avant une chimiothérapie à base de gemcitabine et de carboplatine
Purpose: We report final antitumor efficacy results from a phase II study of trilaciclib, an intravenous cyclin-dependent kinase 4/6 inhibitor, administered prior to gemcitabine plus carboplatin (GCb) in patients with metastatic triple-negative breast cancer (NCT02978716). Experimental design: Patients were randomized (1:1:1) to group 1 (GCb [days 1, 8]; n = 34), group 2 (trilaciclib prior to GCb [days 1, 8]; n = 33), or group 3 (trilaciclib [days 1, 8] and trilaciclib prior to GCb [days 2, 9]; n = 35). Subgroup analyses were performed according to CDK4/6 dependence, level of PD-L1 expression, and RNA-based immune signatures using proportional hazards regression. T-cell receptor (TCR) β CDR3 regions were amplified and sequenced to identify, quantify, and compare the abundance of each unique TCR β CDR3 at baseline and on treatment. Results: Median overall survival (OS) was 12.6 months in group 1, not reached in group 2 (hazard ratio [HR] 0.31; P = 0.0016), 17.8 months in group 3 (HR 0.40; P = 0.0004), and 19.8 months in groups 2 and 3 combined (HR 0.37; P < 0.0001). Efficacy outcomes were comparable regardless of cancer CDK4/6 dependence status and immune signatures. Administering trilaciclib prior to GCb prolonged OS irrespective of PD-L1 status but had greater benefit in the PD-L1-positive population. T-cell activation was enhanced in patients receiving trilaciclib. Conclusions: Administering trilaciclib prior to GCb enhanced antitumor efficacy, with significant improvements in OS. Efficacy outcomes in immunologic subgroups and enhancements in T-cell activation suggest these improvements may be mediated via immunologic mechanisms.