Evaluating the effectiveness of trilaciclib given before chemotherapy in patients with metastatic triple-negative breast cancer.

This study evaluated the effectiveness of trilaciclib (Cosela) given before gemcitabine (Gemzar) plus capecitabine (Xeloda) (GC) chemotherapy regimen in patients with metastatic triple-negative breast cancer (mTNBC). The data showed that trilaciclib given before GC chemotherapy regimen was effective and significantly improved overall survival in these patients.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) that tests negative for female hormone receptors (estrogen and/or progesterone) and the HER2 protein. TNBC accounts for 10-15% of all BCs. It is associated with a poorer disease outcome compared to other subtypes of BC. Treatments for TNBC usually involve a combination of surgery, chemotherapy, and radiotherapy.

Trilaciclib is an inhibitor of the proteins CDK4 and CDK6. They are important in regulating the cell cycle and cell growth. Blocking these proteins slows the growth and spread of cancer cells. It has been recently approved for the treatment of patients with extensive-stage small cell lung cancer. Chemotherapy combination such as GC regimen is recommended for the treatment of mTNBC. However, the effectiveness of trilaciclib given before GC chemotherapy in patients with mTNBC is still unknown.

This study involved 102 patients with mTNBC. Patients were randomly assigned into 3 groups. Group 1 included 34 patients who received GC chemotherapy regimen alone on days 1 and 8. Group 2 included 33 patients who received trilaciclib before GC chemotherapy regimen on days 1 and 8. Group 3 included 35 patients who received trilaciclib alone on days 1 and 8 and trilaciclib before GC chemotherapy regimen on days 2 and 9. The average follow-up time was 8.4 months for group 1, 14 months for group 2, and 15.3 months for group 3.

The average overall survival was not reached in group 2 (exceeded the average follow-up period), 17.8 months in group 3 compared to 12.6 months in group 1. Patients in group 2 were 69% more likely to have a better survival compared to patients in group 1. Patients in group 3 were 60% more likely to have a better survival compared to patients in group 1.

The average overall survival was 19.8 months in groups 2 and 3 combined compared to 12.6 months in group 1. Patients in groups 2 and 3 combined were 63% more likely to have a better survival compared to patients in group 1.

The average survival without cancer worsening was 9.4 months in group 2, 7.3 months in group 3 compared to 5.7 months in group 1. The average survival without cancer worsening was 9 months in groups 2 and 3 combined compared to 5.7 months in group 1.

The objective response rate (ORR; complete or partial disappearance of cancer) was 50% for group 2, 38.7% for group 3 compared to 29.2% for group 1.

Trilaciclib given before GC chemotherapy regimen increased overall survival regardless of PD-L1 status but had a greater benefit in patients with cancer cells positive for PD-L1. T-cell (immune cells) activation was increased in patients receiving trilaciclib.

This study concluded that trilaciclib given before GC chemotherapy regimen was effective and significantly improved overall survival in patients with mTNBC.

The sample size was very small. This study was sponsored by G1 Therapeutics, the manufacturers of trilaciclib.