In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 28, No. 4 ( 2022-02-15), p. 629-636
Abstract:
We report final antitumor efficacy results from a phase II study of trilaciclib, an intravenous cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, administered prior to gemcitabine plus carboplatin (GCb) in patients with metastatic triple-negative breast cancer (NCT02978716). Patients and Methods: 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 programmed death-ligand 1 (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 TCRβ CDR3 at baseline and on treatment. Results: Median overall survival (OS) was 12.6 months in group 1, not reached in group 2 (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 & lt; 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.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.CCR-21-2272
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2022
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
