Dataset Information

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

ABSTRACT:

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 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 < 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.

SUBMITTER: Tan AR

PROVIDER: S-EPMC9377748 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Tan Antoinette R AR Wright Gail S GS Thummala Anu R AR Danso Michael A MA Popovic Lazar L Pluard Timothy J TJ Han Hyo S HS Vojnović Željko Ž Vasev Nikola N Ma Ling L Richards Donald A DA Wilks Sharon T ST Milenković Dušan D Xiao Jie J Sorrentino Jessica J Horton Janet J O'Shaughnessy Joyce J

Clinical cancer research : an official journal of the American Association for Cancer Research 20220201 4

<h4>Purpose</h4>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).<h4>Patients and methods</h4>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 pri ...[more]

PMID: 34887261

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Dataset Information

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

Purpose

Patients and methods

Results

Conclusions

Publications

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

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