The addition of trilaciclib to chemo combinations for
triple-negative breast cancer improves their antitumor effects.
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| Image: Doctor Looking at Mammogram Checking for Breast Cancer | InStyleHealth |
According to the results of a phase II trial,
pretreatment with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor
trilaciclib appears to improve the antitumor efficacy of gemcitabine plus
carboplatin (GCb), with significant survival gains for patients with metastatic
triple-negative breast cancer (mTNBC).
The study comprised 102 adult patients with locally
recurrent/mTNBC who had received at least two prior chemotherapy regimens.
Group 1 received GCb alone on days 1 and 8 (n=34); group 2 received trilaciclib
before to GCb on days 1 and 8 (n=33); and group 3 received trilaciclib alone on
days 1 and 8, and trilaciclib before GCb on days 2 and 9 (n=35). The treatment
took place in 21-day cycles.
Using proportional hazards regression, the researchers
performed subgroup analyses based on CDK4/6 dependency, degree of programmed
death-ligand 1 (PD-L1) expression, and RNA-based immune markers. T-cell
receptor (TCR) CDR3 regions were amplified and sequenced to identify, quantify,
and compare the abundance of each unique TCR CDR3 at baseline and after
therapy.
Group 1 had a median overall survival (OS) of 12.6
months, while group 2 had a median OS of 17.8 months (HR = 0.31; P =). When
compared to chemotherapy alone, add-on trilaciclib reduced the risk of
progression or death by at least 60% in group 2 (HR, 0.31; p=0.0016), group 3
(HR, 0.40; p=0.0004), and groups 2 and 3 combined (HR, 0.37; p0.0001).
Subgroups classified by cancer CDK4/6 dependency
status and immunological markers had similar efficacy findings.
Trilaciclib was given before GCb and improved OS
independent of PD-L1 status, but it was more beneficial in the PD-L1–positive
group. T-cell activation was also increased in patients who were given
trilaciclib.
These gains could be mediated by immunologic pathways,
based on efficacy evidence in immunologic subgroups and improvements in T-cell
activation.