Jared Weiss1, Jerome Goldschmidt2, Zoran Andric3, Konstantin H Dragnev4, Chad Gwaltney5, Konstantina Skaltsa6, Yili Pritchett7, Joyce M Antal7, Shannon R Morris7, Davey Daniel8. 1. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC. Electronic address: jared_weiss@med.unc.edu. 2. Blue Ridge Cancer Care, US Oncology Research, Blacksburg, VA. 3. University Hospital Medical Center Bezanijska Kosa, Bezanijska Kosa, Belgrade, Serbia. 4. Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH. 5. Gwaltney Consulting, Westerly, RI. 6. IQVIA Consulting Services, Barcelona, Spain. 7. G1 Therapeutics, Inc., Research Triangle Park, NC. 8. Sarah Cannon Research Institute, Nashville, TN; Chattanooga Oncology Hematology Associates, Chattanooga, TN.
Abstract
BACKGROUND: Chemotherapy-induced myelosuppression (CIM) and its sequalae cause significant side effects and harm to quality of life. Trilaciclib is an intravenous CDK4/6 inhibitor that is administered prior to chemotherapy to protect hematopoietic stem and progenitor cells from chemotherapy-induced damage (myeloprotection). PATIENTS AND METHODS: Data from three randomized, double-blind, placebo-controlled studies (NCT02499770, NCT03041311, and NCT02514447) were pooled to evaluate the effects of trilaciclib administered prior to standard-of-care chemotherapy (first-line etoposide plus carboplatin [E/P], first-line E/P plus atezolizumab, and second-/third-line topotecan) in patients with extensive-stage small cell lung cancer (ES-SCLC). The primary endpoints were duration of severe neutropenia (absolute neutrophil count < 0.5 × 109 cells/L) in cycle 1 and occurrence of severe neutropenia. Additional prespecified endpoints further assessed the effect of trilaciclib on myeloprotection, health-related quality of life (HRQoL), antitumor efficacy, and safety. RESULTS: Of 242 randomized patients, 123 received trilaciclib and 119 received placebo. Compared with placebo, administration of trilaciclib prior to chemotherapy resulted in significant decreases in most measures of multilineage CIM. The reduction in hematologic toxicity translated into the reduced need for supportive care interventions and hospitalizations due to CIM or sepsis and improvements in HRQoL domains related to the protected cell lineages, including fatigue, physical wellbeing, and functional wellbeing. Antitumor efficacy was similar for patients receiving trilaciclib or placebo. CONCLUSION: Administering trilaciclib prior to chemotherapy resulted in clinically meaningful reductions in CIM and its consequences and improved patient HRQoL, with no impact on the antitumor efficacy of three individual chemotherapy regimens used in the first- or second-/third-line treatment of ES-SCLC.
BACKGROUND: Chemotherapy-induced myelosuppression (CIM) and its sequalae cause significant side effects and harm to quality of life. Trilaciclib is an intravenous CDK4/6 inhibitor that is administered prior to chemotherapy to protect hematopoietic stem and progenitor cells from chemotherapy-induced damage (myeloprotection). PATIENTS AND METHODS: Data from three randomized, double-blind, placebo-controlled studies (NCT02499770, NCT03041311, and NCT02514447) were pooled to evaluate the effects of trilaciclib administered prior to standard-of-care chemotherapy (first-line etoposide plus carboplatin [E/P], first-line E/P plus atezolizumab, and second-/third-line topotecan) in patients with extensive-stage small cell lung cancer (ES-SCLC). The primary endpoints were duration of severe neutropenia (absolute neutrophil count < 0.5 × 109 cells/L) in cycle 1 and occurrence of severe neutropenia. Additional prespecified endpoints further assessed the effect of trilaciclib on myeloprotection, health-related quality of life (HRQoL), antitumor efficacy, and safety. RESULTS: Of 242 randomized patients, 123 received trilaciclib and 119 received placebo. Compared with placebo, administration of trilaciclib prior to chemotherapy resulted in significant decreases in most measures of multilineage CIM. The reduction in hematologic toxicity translated into the reduced need for supportive care interventions and hospitalizations due to CIM or sepsis and improvements in HRQoL domains related to the protected cell lineages, including fatigue, physical wellbeing, and functional wellbeing. Antitumor efficacy was similar for patients receiving trilaciclib or placebo. CONCLUSION: Administering trilaciclib prior to chemotherapy resulted in clinically meaningful reductions in CIM and its consequences and improved patient HRQoL, with no impact on the antitumor efficacy of three individual chemotherapy regimens used in the first- or second-/third-line treatment of ES-SCLC.
Authors: Maen Hussein; Marina Maglakelidze; Donald A Richards; Marielle Sabatini; Todd A Gersten; Keith Lerro; Ivan Sinielnikov; Alexander Spira; Yili Pritchett; Joyce M Antal; Rajesh Malik; J Thaddeus Beck Journal: Cancer Manag Res Date: 2021-08-09 Impact factor: 3.989
Authors: Renata Ferrarotto; Ian Anderson; Balazs Medgyasszay; Maria Rosario García-Campelo; William Edenfield; Trevor M Feinstein; Jennifer M Johnson; Sujith Kalmadi; Philip E Lammers; Alfredo Sanchez-Hernandez; Yili Pritchett; Shannon R Morris; Rajesh K Malik; Tibor Csőszi Journal: Cancer Med Date: 2021-08-18 Impact factor: 4.452