Trilaciclib May Help Protect Against Chemotherapy Damage in Small Cell Lung Cancer

Trilaciclib significantly reduced chemotherapy-induced myelosuppression (CIM) in patients with extensive-stage small cell lung cancer (SCLC), according to a pooled analysis published in Cancer Treatment and Research Communications.¹

Administered before chemotherapy, the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor significantly reduced the incidence of severe neutropenia (SN) and associated complications, which the authors said offers a promising approach to managing the toxic effects of chemotherapy while maintaining treatment efficacy.

Trilaciclib significantly reduced chemotherapy-induced myelosuppression in extensive-stage SCLC. | Image credit: Photographee.eu – stock.adobe.com

“Patients with ES-SCLC are likely to benefit from chemotherapy if they can tolerate it and undergo complete treatment cycles,” the authors said. “In this pool analysis, with a lower incidence of cycle delays, dose reductions were observed with a higher RDI [relative dose intensity] in the trilaciclib group than in the placebo group, which may not compromise the chemotherapeutic efficacy.”

The study included 325 patients from China and western countries who were randomized to receive trilaciclib or placebo prior to chemotherapy. Compared with placebo, trilaciclib substantially lowered the duration of SN in the first cycle of chemotherapy and reduced the incidence of SN and febrile neutropenia (FN).

In first-line treatment settings, the incidence of SN dropped from 41.6% in the placebo group to just 2.7% in the trilaciclib group. According to the authors, these reductions in CIM highlight trilaciclib’s ability to protect hematopoietic stem and progenitor cells during chemotherapy by temporarily arresting their cell cycle, enabling them to recover and function normally.

“The current pooled analysis included the largest data set from four randomized clinical trials encompassing patients from China and western countries,” the authors said. “Trilaciclib before chemotherapy provides protection from chemotherapy-induced myelosuppression in multilineage blood cells across different treatment lines and reduces the need for supportive care with a good safety profile.”

Patients receiving trilaciclib also experienced fewer FN episodes, reduced need for supportive care interventions such as granulocyte-colony stimulating factors (G-CSF) and red blood cell transfusions, and lower rates of grade 3 and 4 anemia. The results were consistent across all treatment lines.

Median progression-free survival (PFS) and overall survival (OS) were comparable between the trilaciclib and placebo groups, with trilaciclib showing a median PFS of 5.3 months vs 4.9 months and a median OS of 10.9 months vs 10.1 months. The treatment was well tolerated, with similar rates of serious treatment-emergent adverse events (TEAEs) between groups and fewer cases of infection or antibiotic use in the trilaciclib group compared with placebo. The most common TEAEs were decreases in neutrophil, white blood, and platelet counts, as well as anemia.

Chemotherapy-induced myelosuppression remains a significant challenge in extensive-stage SCLC care, often leading to dose reductions, treatment delays, and increased health care utilization. According to the study authors, trilaciclib addresses these issues by reducing the severity and frequency of CIM, allowing patients to maintain uninterrupted treatment cycles and minimizing the risk of complications like FN, which often require hospitalization. They noted the benefits of trilaciclib extend beyond myeloprotection, as it facilitates a more tolerable chemotherapy experience while maintaining treatment efficacy.

They also explained what sets it apart from the 3 other FDA-approved CDK4/6 inhibitors: palbociclib, ribociclib, and abemaciclib. Aside from being approved for bone marrow protection in extensive-stage SCLC, trilaciclib is administered intravenously before chemotherapy, whereas the other 3 are oral drugs given continuously.² Trilaciclib also has a shorter time to peak plasma concentration and half-life, acting faster but only during chemotherapy, while the others continuously inhibit CDK4/6, leading to longer pharmacodynamic effects.³

“Therefore, it is due to the difference in mechanism of action, half-life, dosing regimen that trilaciclib can exert bone marrow protection effects promptly during chemotherapy treatment, while the other three oral CDK4/6 inhibitors, due to continuous inhibition of the bone marrow, their main adverse events are hematological toxicities,” the authors said.¹

References

1. Liu Y, Wu L, Huang D, et al. Effect of trilaciclib administered before chemotherapy in patients with extensive-stage small-cell lung cancer: A pooled analysis of four randomized studies. Cancer Treat Res Commun. Published online January 10, 2025. doi:10.1016/j.ctarc.2025.100869
2. Patel TI, Joshi JN, Valvezan AJ, et al. A review of trilaciclib, a first-in-class cyclin-dependent kinase 4/6 inhibitor, for the management of metastatic small-cell lung cancer. Med Chem Res. Published online July 26, 2024. doi:10.1007/s00044-024-03288-y
3. Young JA, Tan AR. Trilaciclib: a first-in-class therapy to reduce chemotherapy-induced myelosuppression. touchREVIEWS in Oncology & Haematology. Published online August 1, 2022. doi:10.17925/OHR.2022.18.2.152