The FDA has approved trilaciclib (CoselaTM, G1 Therapeutics) for the prevention of myelosuppression in patients receiving chemotherapy for extensive-stage small-cell lung cancer (SCLC). Occurring when chemotherapy agents damage the bone marrow, myelosuppression decreases the production of red blood cells, white blood cells, and platelets, causing patients to experience fatigue, bleeding, and increased risk of infection.
"Chemotherapy is a mainstay of cancer treatment; however, its side effects, notably myelosuppression, cause significant suffering," write the authors of a pooled analysis of three trials on which the approval was based, led by Jared Weiss, MD, Associate Professor of Medicine at the University of North Carolina's Lineberger Comprehensive Cancer Center, in their presentation abstract from the American Society of Clinical Oncology (ASCO) 2020 Annual Meeting. "Trilaciclib is an intravenous CDK4/6 inhibitor that protects hematopoietic stem and progenitor cells by preventing proliferation during chemotherapy administration."
The three studies (NCT03041311, NCT0249970, and NCT02514447) enrolled a total of 245 patients with extensive-stage SCLC. All patients received standard chemotherapy, consisting of etoposide/carboplatin, etoposide/carboplatin/atezolizumab, or topotecan, with the addition of either trilaciclib or placebo administered intravenously prior to chemotherapy. The primary end points of the pooled analysis were the incidence and duration of myelosuppression, including severe and febrile neutropenia, and the need for supportive care measures.
Trilaciclib significantly reduced the incidence of severe neutropenia (11.4% vs 52.9%), febrile neutropenia (3.3% vs 9.2%), grade 3/4 anemia (20.3% vs 31.9%), and grade 3/4 thrombocytopenia (19.5% vs 36.1%) compared with placebo. Patients receiving trilaciclib also experienced a decreased need for supportive care interventions, including granulocyte colony-stimulating factor (GCSF) administration (28.5% vs 56.3%), red blood cell transfusion on or after Week 5 of treatment (14.6% vs 26.1%), erythropoiesis-stimulating agent administration (3.3% vs 11.8%), and platelet transfusion (8.1% vs 9.2%). Median overall survival was 10.6 months in both treatment arms, with a similar median progression-free survival between the trilaciclib and placebo groups (5.3 vs 5.0 months).
Grade 3 or higher hematologic events occurred in fewer patients receiving trilaciclib compared with placebo (44.3% vs 77.1%). Among patients who received more than one cycle of chemotherapy, 9.2% of those in the trilaciclib group required at least one chemotherapy dose reduction compared with 30.8% of those in the placebo group. The most common adverse events occurring in patients receiving trilaciclib included fatigue, headache, pneumonia, increased levels of aspartate aminotransferase, and decreased levels of calcium, potassium, and phosphate. The prescribing information for trilaciclib notes that injection site reactions, acute drug hypersensitivity, interstitial lung disease/pneumonitis, and embryo-fetal toxicity may also occur.
"Trilaciclib significantly and meaningfully reduced both chemotherapy-induced myelosuppression and its consequences, with no detrimental effect on progression-free survival or overall survival, thus improving the patient experience with chemotherapy in extensive-stage SCLC," concluded Dr. Weiss and colleagues. "Trilaciclib has the potential to become a new standard of care for preventing myelosuppression in SCLC."
The recommended dose of trilaciclib is 240 mg/m2 administered intravenously over 30 minutes, completed within four hours prior to the start of each chemotherapy treatment.
For More Information
Weiss J, Goldschmidt J, Zoran A, et al (2020). Myelopreservation and reduced use of supportive care with trilaciclib in patients with small cell lung cancer. J Clin Oncol (ASCO Virtual Scientific Program Abstracts), 38(suppl_15). Abstract 12096. DOI:10.1200/JCO.2020.38.15_suppl.12096
Clinicaltrials.gov (2021). Carboplatin, etoposide, and atezolizumab with or without trilaciclib (G1T28), a CDK 4/6 inhibitor, in extensive stage small cell lung cancer (SCLC). NLM identifier: NCT03041311.
US Food & Drug Administration (2021). FDA approves drug to reduce bone marrow suppression caused by chemotherapy. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-drug-reduce-bone-marrow-suppression-caused-chemotherapy
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