Naslov
Trilaciclib Prior to Chemotherapy in Patients with Metastatic Triple-Negative Breast Cancer: Final Efficacy and Subgroup Analysis from a Randomized Phase II Study

Autori
Tan, Antoinette R. ; Wright, Gail S. ; Thummala, Anu R. ; Danso, Michael A. ; Popovic, Lazar ; Pluard, Timothy J. ; Han, Hyo S. ; Vojnović, Željko ; Vasev, Nikola ; Ma, Ling ; Richards, Donald A. ; Wilks, Sharon T. ; Milenkovic, Dusan ; Xiao, Jie ; Sorrentino, Jessica ; Horton, Janet ; O'Shaughnessy, Joyce

Izvornik
Clinical cancer research (1078-0432) 28 (2022), 4; 629-636

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Antineoplastic Combined Chemotherapy Protocols Humans Pyrimidines / therapeutic use Pyrroles / therapeutic use Triple Negative Breast Neoplasms* / pathology

Sažetak
Purpose: 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 carbo-platin (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 sig-natures using proportional hazards regression. T-cell receptor (TCR) (3 CDR3 regions were amplified and sequenced to identify, quantify, and compare the abundance of each unique TCR(3 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 < 0.0001). Efficacy outcomes were comparable regardless of cancer CDK4/6 dependence status and immune signatures. Adminis-tering 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. onclusions: 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 immu-nologic mechanisms.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

Napomena
G1 Therapeutics, Inc.

POVEZANOST RADA