OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Trilaciclib – Cosela®

DRUG CLASS

Antineoplastic Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Trilaciclib	1374743-00-6	C24-H30-N8-O

ANNOTATED BIBLIOGRAPHY

References updated: 17 October 2023

Abbreviations: ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; PR, progesterone receptor.

• Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Review of hepatotoxicity published in 1999 before the availability of protein kinase inhibitors).
• DeLeve LD. Kinase inhibitors. Cancer chemotherapy. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, p. 556.

  (Review of hepatotoxicity of cancer chemotherapeutic agents, does not discuss trilaciclib).
• Wellstein A, Giaccone G, Atkins MB, Sausville EA. Pathway targeted therapies: monoclonal antibodies, protein kinase inhibitors, and various small molecules. In, Brunton LL Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 1203-36.

  (Textbook of pharmacology and therapeutics).
• FDA. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2020/214200Orig1s000SumR.pdf

  (FDA website with initial product label and multidiscipline review of the safety and efficacy of trilaciclib describes 240 patients treated with trilaciclib [122] vs placebo [118] in whom deaths occurred in 75% of each group, serious adverse events in 30% vs 25%, febrile neutropenia 3% vs 6%, any infection 7% vs 10%, fatigue 34% vs 27%, hypocalcemia 24% vs 21%, hypokalemia 22% vs 18%, AST elevations 17% vs 14%, headache 13% vs 9%, infusion site reactions 13% vs 3%, rash 9% vs 6%, and thrombophlebitis 4% vs <1%; no mention of clinically apparent liver injury or deaths from liver failure).
• Tan AR, Wright GS, Thummala AR, Danso MA, Popovic L, Pluard TJ, Han HS, et al. Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic trip le-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial. Lancet Oncol. 2019;20:1587-1601. [PubMed: 31575503]

  (Among 102 adults with recurrent or metastatic triple negative breast cancer treated with gemcitabine and carboplatin with or without one of two regimens of trilaciclib, indices of myelosuppression and rates of febrile neutropenia were similar in all groups; no mention of ALT elevations or hepatotoxicity).
• Hart LL, Ferrarotto R, Andric ZG, Beck JT, Subramanian J, Radosavljevic DZ, Zaric B, et al. Myelopreservation with trilaciclib in patients receiving topotecan for small cell lung cancer: results from a randomized, double-blind, placebo-controlled phase II study. Adv Ther. 2021;38:350-365. [PMC free article: PMC7854399] [PubMed: 33123968]

  (Among 61 adults with extensive small cell lung cancer treated with topotecan [days 1 to 5 of 21-day cycles] with or without pretreatment with trilaciclib, serious neutropenia was less frequent [41% vs 76%] and shorter in duration [median 1 vs 7 days] as were rates of thrombocytopenia [63% vs 68%] and anemia [53% vs 61%] while side effect rates were usually similar [except headache at 41% vs 36%]; no mention of infusion reactions, ALT elevations or hepatotoxicity).
• Daniel D, Kuchava V, Bondarenko I, Ivashchuk O, Reddy S, Jaal J, Kudaba I, et al. Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: A multicentre, randomised, double-blind, placebo-controlled Phase II trial. Int J Cancer. 2020;148:2557–70. [PMC free article: PMC8048941] [PubMed: 33348420]

  (Among 105 adults with advanced or metastatic small cell lung cancer treated with trilaciclib vs placebo at the time of intravenous platin/etoposide-based chemotherapy, the rate of severe neutropenia was 1.9% vs 49% and duration of neutropenia 0 vs 4 days, while adverse events were mostly mild and transient, AST elevations arising in 12% vs 4% and being above 5 times ULN in 2% vs none, but there were no liver related discontinuations or fatalities).
• Dhillon S. Trilaciclib: first approval. Drugs. 2021;81(7):867-874. [PubMed: 33861388]

  (Review of the structure, mechanism of action, history of development, pharmacokinetics, clinical efficacy, and safety of trilaciclib shortly after its approval in the US, the first agent approved for prophylaxis against chemotherapy induced myelosuppression).
• Roskoski R Jr. Properties of FDA-approved small molecule protein kinase inhibitors: a 2022 update. Pharmacol Res. 2022;175:106037. [PubMed: 34921994]

  (Comprehensive review of human protein kinases and the 68 small molecular inhibitors that have been approved for use in neoplastic [n=58], autoimmune, cardiovascular, neurologic, and inflammatory diseases; the 68 drugs can be categorized as serine/threonine [n=12], tyrosine [n=42], or dual [n=4] kinase inhibitors, and as tyrosine receptor [n=39] or nonreceptor [n=13] inhibitors; trilaciclib is a non-receptor tyrosine kinase inhibitor and unlike most kinase protein inhibitors is given intravenously to achieve high levels of inhibition of hematopoietic cells to protect them against the cytotoxicity of anticancer drugs, a controversial issue being whether it also protects cancer cell from the cytotoxicity).
• Trilaciclib (Cosela) for prevention of chemotherapy-related myelosuppression. Med Lett Drugs Ther. 2021;63:174-175. [PubMed: 35085207]

  (Concise review of the mechanism of action, clinical efficacy, safety, and cost of trilaciclib shortly after its approval in the US mentions that AST elevations occur in more than 10% of treated patients).
• Goel S, Tan AR, Rugo HS, Aftimos P, Andrić Z, Beelen A, Zhang J, et al. Trilaciclib prior to gemcitabine plus carboplatin for metastatic triple-negative breast cancer: phase III PRESERVE 2. Future Oncol. 2022;18:3701-3711. [PubMed: 36135712]

  (Rationale for and design of a phase 3 placebo-controlled trial of trilaciclib in adults with metastatic breast cancer negative for estrogen, progesterone and human epidermal growth factor 2 receptors).