In a phase II trial reported in The Lancet Oncology, Tan et al found that the addition of the cell-cycle inhibitor trilaciclib to gemcitabine/carboplatin chemotherapy did not reduce the duration or incidence of severe neutropenia during chemotherapy in women with triple-negative breast cancer. A potential survival benefit was observed in patients receiving trilaciclib.
A noted by the investigators, by transiently maintaining immune cells and hematopoietic stem and progenitor cells in G1 arrest, trilaciclib may protect immune cells and bone marrow from chemotherapy-induced damage, thereby optimizing antitumor activity while minimizing myelotoxicity.
Study Details
The open-label study included 102 patients from 33 sites in five countries (26 sites in the United States). They were randomly assigned 1:1:1 between February 2017 and May 2018 to receive gemcitabine 1000 mg/m2 and intravenous carboplatin (area under the concentration-time curve 2 μg × h/mL) on days 1 and 8 (group 1, n = 34), gemcitabine/carboplatin plus intravenous trilaciclib 240 mg/m2 on days 1 and 8 (group 2, n = 33), or gemcitabine/carboplatin on days 2 and 9 plus trilaciclib on days 1, 2, 8, and 9 (group 3, n = 35) of 21-day cycles. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent, or discontinuation by the investigator. The primary endpoints were duration of severe (grade 4) neutropenia during cycle 1 and incidence of severe neutropenia during the treatment period. Overall, 37% of patients had had received one or two lines of previous chemotherapy in the metastatic setting.
KEY POINTS
- Use of trilaciclib was not associated with reduced duration or incidence of severe neutropenia.
- Overall survival appeared to be prolonged in patients receiving trilaciclib.
Treatment Outcomes
Median follow-up was 8.4 months for group 1, 12.7 months for group 2, and 12.9 months for group 3. During cycle 1, mean durations of severe neutropenia were 0.8 days in group 1, 1.5 days in group 2, and 1.0 days in group 3 (P = .70 for group 3 vs group 1). During the course of treatment, severe neutropenia occurred in 9 (26%) of 34 patients in group 1, 12 (36%) of 33 in group 2, and 8 (23%) of 35 in group 3 (P = .70 for group 3 vs group 1).
Median progression-free survival was 5.7 months in group 1, 9.4 months in group 2, and 7.3 months in group 3, with no significant differences observed between groups 2 or 3 vs group 1.
Median overall survival was 12.6 months, 20.1 months (P = .028 vs group 1), and 17.8 months (P = .0023 vs group 1).
Adverse Events
The most common adverse events of any grade were anemia (73%), neutropenia (70%), and thrombocytopenia (60%) in group 1; neutropenia (82%), thrombocytopenia (55%), and anemia (52%) in group 2; and neutropenia (66%), thrombocytopenia (63%), and nausea (49%) in group 3. No treatment-related deaths were observed.
The investigators concluded, “No significant differences were observed in myelosuppression endpoints with trilaciclib plus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer; however, the regimen was generally well tolerated and overall survival results were encouraging. Further studies of trilaciclib in this setting are warranted.”
Antoinette R. Tan, MD, of Levine Cancer Institute, Atrium Health, Charlotte, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by G1 Therapeutics. For full disclosures of the study authors, visit thelancet.com.
