Myeloprotective Effects of Trilaciclib Among Patients with Small Cell Lung Cancer at Increased Risk of Chemotherapy-Induced Myelosuppression: Pooled Results from Three Phase 2, Randomized, Double-Blind, Placebo-Controlled Studies

• Published in: Cancer management and research Vol. 13; pp. 6207 - 6218
• Main Authors: Hussein, Maen, Maglakelidze, Marina, Richards, Donald A, Sabatini, Marielle, Gersten, Todd A, Lerro, Keith, Sinielnikov, Ivan, Spira, Alexander, Pritchett, Yili, Antal, Joyce M, Malik, Rajesh, Beck, J Thaddeus
• Format: Journal Article
• Language: English
• Published: Macclesfield Dove Medical Press Limited 01-01-2021; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Age; Anemia; Bone marrow; Cancer therapies; Carboplatin; Cardiovascular disease; Cell cycle; Chemotherapy; Clinical trials; Comorbidity; Cyclin-dependent kinases; Cytotoxicity; Double-blind studies; Growth factors; Health aspects; Hematopoietic stem cells; Hemoglobin; HIV; Human immunodeficiency virus; Infections; Kinases; Lung cancer; Lung cancer, Small cell; myelopreservation; myeloprotection; myelosuppression; Neutropenia; Neutrophils; Nutritional status; Oncology; Original Research; Patients; Pharmaceutical industry; Product development; Risk factors; small cell lung cancer; trilaciclib; United States; United Kingdom
• ISSN: 1179-1322; 1179-1322
• DOI: 10.2147/CMAR.S313045

Purpose: Trilaciclib is an intravenous cyclin-dependent kinase 4/6 inhibitor indicated to decrease the incidence of chemotherapy-induced myelosuppression (CIM) by protecting hematopoietic stem and progenitor cells and immune system function from chemotherapy-induced damage (myeloprotection). Here, we investigated the myeloprotective effects of trilaciclib among patients at increased risk of CIM. Patients and Methods: Data were pooled from three randomized, double-blind, placebo-controlled, phase 2 clinical studies of trilaciclib administered prior to chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). Myeloprotective outcomes were evaluated in patient subgroups based on age (<65 or [greater than or equal to]65 years), risk of chemotherapy-induced febrile neutropenia (FN), and risk of anemia or red blood cell (RBC) transfusions. For the FN and anemia analyses, risk factors were identified from published literature and used to classify patients into FN and anemia risk categories. Subgroup analysis based on age was also performed on patient reported outcome (PRO) measures. Results: In total, 123 patients received trilaciclib and 119 patients received placebo. Myeloprotective benefits of trilaciclib were observed regardless of age, with greater effects observed among patients aged [greater than or equal to]65 years. Across FN risk factors and categories, trilaciclib had beneficial effects on neutrophil-related endpoints vs placebo, with greater effects observed in patients at higher risk of FN. Effects on RBC-related endpoints favored trilaciclib vs placebo, regardless of anemia risk factors and categories. Improvements in PROs with trilaciclib were observed irrespective of age group, but with greater improvements and less deterioration from baseline observed in older patients. Conclusion: By both decreasing the incidence of CIM and improving quality of life, trilaciclib has the potential to allow patients receiving chemotherapy for ES-SCLC, including patients who are older or more vulnerable to CIM, to receive chemotherapy on schedule and at standard-of-care doses, and to improve the experience for patients receiving chemotherapy to treat ES-SCLC. Clinical Trial Numbers: NCT02499770; NCT03041311; NCT02514447. Keywords: trilaciclib, myelosuppression, myeloprotection, myelopreservation, chemotherapy, small cell lung cancer