Add-on trilaciclib boosts antitumour effects of chemo combinations for triple-negative breast cancer

Pretreatment with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor trilaciclib appears to enhance the antitumour efficacy of gemcitabine plus carboplatin (GCb), with significant survival gains for patients with metastatic triple-negative breast cancer (mTNBC), according to the results of a phase II trial.

The trial included 102 adult patients who had received at least two prior chemotherapy regimens for locally recurrent/mTNBC. They were randomly assigned to one of the following treatment groups: group 1 received GCb alone on days 1 and 8 (n=34); group 2 received trilaciclib prior 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). Treatment was given in 21-day cycles.

Researchers performed subgroup analyses according to CDK4/6 dependence, level of programmed death-ligand 1 (PD-L1) expression, and RNA-based immune signatures using proportional hazards regression. They amplified and sequenced T-cell receptor (TCR) β CDR3 regions 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 =), 17.8 months in. Add-on trilaciclib reduced the risk of progression or death by at least 60 percent in group 2 (hazard ratio [HR], 0.31; p=0.0016), group 3 (HR, 0.40; p=0.0004), and groups 2 and 3 combined (HR, 0.37; p<0.0001) as compared with chemotherapy alone.

Efficacy outcomes were similar across subgroups defined by cancer CDK4/6 dependence status and immune signatures.

Administering trilaciclib prior to GCb improved OS regardless of PD-L1 status but had greater benefit in the PD-L1–positive population. Moreover, T-cell activation was enhanced in groups of patients who received trilaciclib.

The efficacy data in immunologic subgroups and enhancements in T-cell activation indicate that these improvements may be mediated via immunologic mechanisms.