The combination of trilaciclib and chemotherapy was generally well–tolerated with promising activity in a phase II trial of patients with metastatic triple-negative breast cancer. However, it did not offer improvements in measures of myelosuppression compared with chemotherapy alone.
“Chemotherapy-induced myelosuppression commonly leads to dose reductions that can restrict therapeutic dose intensity,” wrote study authors led by Antoinette R. Tan, MD, of the Levine Cancer Institute in Charlotte, North Carolina. “Introducing therapy that can protect the immune cells and bone marrow from the cytotoxic effects of chemotherapy has the potential to optimize antitumour activity while minimizing myelotoxicity.”
Triliciclib is an inhibitor of cyclin-dependent kinases-4/6; it can enhance antitumor immunity and preserve hematopoietic stem and progenitor cells during chemotherapy. The new phase II study included a total of 142 patients with metastatic triple-negative breast cancer randomized to receive either gemcitabine (Gemzar) plus carboplatin alone (group 1) or 1 of 2 regimens with those agents plus trilaciclib. One regimen included intravenous trilaciclib along with the chemotherapy agents on days 1 and 8 of 21-day cycles (group 2), while the other included gemcitabine and carboplatin on days 2 and 9 along with trilaciclib on days 1, 2, 8, and 9 (group 3). The results of the study were published online ahead of print on September 28 in Lancet Oncology.
The median follow-up for the three groups was 8.4 months, 12.7 months, and 12.9 months, respectively. During the first cycle, the mean duration of severe neutropenia was 0.8 days in the chemotherapy alone group, 1.5 days in group 2, and 1.0 days in group 3; these differences were not significant.
A total of 9 of 34 patients (26%) in group 1, compared with 12 of 33 patients (36%) in group 2 and eight of 35 patients (23%) in group 3 (P = 0.70). There were no differences between the groups with regard to all-cause dose reductions, patients requiring G-CSF, or patients requiring red blood cell transfusion, among other outcomes. The most common treatment-emergent adverse events included anemia, neutropenia, and thrombocytopenia in groups 1 and 2, and in group 3 they included neutropenia, thrombocytopenia, and nausea.
Overall survival outcomes in the 2 trilaciclib groups were significantly better than in the chemotherapy alone group. The combined trilaciclib groups had a median OS of 20.1 months, compared with 12.6 months without trilaciclib.
Though the trilaciclib regimens did not show significant improvements with regard to myelosuppression compared with chemotherapy, the authors highlighted the improvement in anti-tumor activity.
“Together with the safety profile reported, the clinically meaningful improvements in overall survival support further studies of trilaciclib in patients with metastatic triple-negative breast cancer,” they wrote.