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.
Another trial with neoadjuvant immunotherapy showing improved results over chemotherapy alone. (12% higher PCR 48% vs 36%).
Dato-DXd is now approved in HR+, HER2-neg, metastatic breast cancer after prior therapy with endocrine-based therapy and chemotherapy. There was an impressive reduction in the risk of death or progression with an HR of 0.63. Watch out for ocular and pulmonary toxicity. HER2-ultra low testing will be burdensome but must be done for drug approval.
TD beat chemotherapy after failure of hormonal therapy in HER-2 low and ultra low. Wait for the indication.
MammaPrint did not predict distant recurrence, but it did predict patients who may benefit from extended hormonal therapy. We do have breast index, so now we have options. Breast index can predict the possibility of recurrence though by helping to determine the level of risk.
This study confirms what we saw in initial reports showing the addition of pembro increasing the rate of ypathological complete response (ypCR’s) in the neoadjuvant setting for triple-negative breast cancer (TNBC). New data shows a 5% improvement (87 vs 82%) in overall survival (OS) with the quadruplet. Higher gains but at higher cost of toxicity. The fact that adjuvant intraosseous (IO) does not seem to improve outcomes, but neoadjuvant chemo+IO does show intact tumor-immune interactions to create maximum treatment effectiveness is most likely real. Of note, this seems mostly independent of programmed death-ligand 1 (PDL1) status.
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