Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Study.

Autor: Hart LL; Medical Oncology, Florida Cancer Specialists, Fort Myers, FL, USA. lhart@flcancer.com.; Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA. lhart@flcancer.com., Ferrarotto R; Department of Thoracic and Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Andric ZG; Medical Oncology Department, Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia., Beck JT; Department of Medical Oncology and Hematology, Highlands Oncology Group, Rogers, MI, USA., Subramanian J; Department of Medicine, Saint Luke's Hospital, Kansas City, MO, USA., Radosavljevic DZ; Institute for Oncology and Radiology of Serbia, Belgrade, Serbia., Zaric B; Faculty of Medicine, Institute for Pulmonary Diseases of Vojvodina, University of Novi Sad, Sremska Kamenica, Serbia., Hanna WT; Hematology/Oncology, University of Tennessee Graduate School of Medicine, Knoxville, TN, USA., Aljumaily R; Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA.; Sarah Cannon Research Institute, Nashville, TN, USA., Owonikoko TK; Department of Hematology and Medical Oncology, Emory University, Atlanta, GA, USA., Verhoeven D; Department of Medical Oncology, AZ Klina Brasschaat, University of Antwerp, Antwerp, Belgium., Xiao J; G1 Therapeutics, Inc., Research Triangle Park, NC, USA., Morris SR; G1 Therapeutics, Inc., Research Triangle Park, NC, USA., Antal JM; G1 Therapeutics, Inc., Research Triangle Park, NC, USA., Hussein MA; Department of Oncology, Florida Cancer Specialists, Leesburg, FL, USA.
Jazyk: angličtina
Zdroj: Advances in therapy [Adv Ther] 2021 Jan; Vol. 38 (1), pp. 350-365. Date of Electronic Publication: 2020 Oct 29.
DOI: 10.1007/s12325-020-01538-0
Abstrakt: Introduction: Multilineage myelosuppression is an acute toxicity of cytotoxic chemotherapy, resulting in serious complications and dose modifications. Current therapies are lineage specific and administered after chemotherapy damage has occurred. Trilaciclib is a cyclin-dependent kinase 4/6 inhibitor that is administered prior to chemotherapy to preserve hematopoietic stem and progenitor cells and immune system function during chemotherapy (myelopreservation).
Methods: In this randomized, double-blind, placebo-controlled phase II trial, patients with previously treated extensive-stage small cell lung cancer (ES-SCLC) were randomized to receive intravenous trilaciclib 240 mg/m 2 or placebo before topotecan 1.5 mg/m 2 on days 1-5 of each 21-day cycle. Primary endpoints were duration of severe neutropenia (DSN) in cycle 1 and occurrence of severe neutropenia (SN). Additional endpoints were prespecified to further assess the effect of trilaciclib on myelopreservation, safety, patient-reported outcomes (PROs), and antitumor efficacy.
Results: Thirty-two patients received trilaciclib, and 29 patients received placebo. Compared with placebo, administration of trilaciclib prior to topotecan resulted in statistically significant and clinically meaningful decreases in DSN in cycle 1 (mean [standard deviation] 2 [3.9] versus 7 [6.2] days; adjusted one-sided P < 0.0001) and occurrence of SN (40.6% versus 75.9%; adjusted one-sided P = 0.016), with numerical improvements in additional neutrophil, red blood cell, and platelet measures. Patients receiving trilaciclib had fewer grade ≥ 3 hematologic adverse events than patients receiving placebo, particularly neutropenia (75.0% versus 85.7%) and anemia (28.1% versus 60.7%). Myelopreservation benefits extended to improvements in PROs, specifically in those related to fatigue. Antitumor efficacy was comparable between treatment arms.
Conclusions: Compared with placebo, the addition of trilaciclib prior to topotecan for the treatment of patients with previously treated ES-SCLC improves the patient experience of receiving chemotherapy, as demonstrated by a reduction in chemotherapy-induced myelosuppression, improved safety profile, improved quality of life and no detrimental effects on antitumor efficacy.
Trial Registration: ClinicalTrials.gov: NCT02514447.
Databáze: MEDLINE
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