Gail Lynn Shaw Wright, MD, FACP, FCCP is co-author of this study that examines the efficacy of administering Trilaciclib prior to chemotherapy in patients with metastatic triple-negative breast cancer.
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 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.
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.
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.
Would you keep treating with CDK4/6 inhibitors and just switch endocrine therapy after failing first line ET+CDK4/6 inhibitor? This trial says YES….
For radiation oncologists: omitting radiation in patients with favorable features of 55 years of age and older.
It seems that PET is better than CT scan in locally advanced disease staging, better in upstaging, and may spare the patient combined modality therapy.
Capivasertib + fulvestrant was superior to fulvestrant alone in HR+ MBC with prior failure of AI with or without a CDK4/6 inhibitor. This is an AKT-pathway inhibitor; main SEs were rash and diarrhea in the experimental arm. Combo to keep in mind for the future, yet to be approved by the FDA.
Interesting approach where endocrine therapy was changed after progression on 1L therapy and the ribociclib was continued.
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