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

• Type of Material: Article
• Authors: Lowell L. Hart, Florida Cancer Specialists; Renata Ferrarotto, University of Texas MD Anderson Cancer Center; Zoran G. Andric, Clinical Hospital Center Bezanijska Kosa; J. Thaddeus Beck, Highlands Oncology Group; Janakiraman Subramanian, St Lukes Hospital; Davorin Z. Radosavljevic, Institute for Oncology and Radiology of Serbia; Bojan Zaric, University of Novi Sad; Wahid T. Hanna, University of Tennessee; Raid Aljumaily, University of Oklahoma; Taofeek Owonikoko, Emory University; Didier Verhoeven, University of Antwerp; Jie Xiao, G1 Therapeutics Inc; Shannon R. Morris, G1 Therapeutics Inc; Joyce M. Antal, G1 Therapeutics Inc; Maen A. Hussein, Florida Cancer Specialists
• Language: English
• Date: 2020-10-29
• Publisher: SPRINGER
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1007/s12325-020-01538-0
• Title of Journal or Parent Work: ADVANCES IN THERAPY
• Volume: 38
• Issue: 1
• Start Page: 350
• End Page: 365
• Grant/Funding Information: This study and medical writing support, along with the Rapid Service and Open Access fees, were funded by G1 Therapeutics, Inc. (Research Triangle Park, NC).
• Keywords: FUNCTIONAL ASSESSMENT; THERAPY; Topotecan; ANCHOR; Research & Experimental Medicine; Pharmacology & Pharmacy; SURVIVAL; RISK; Neutropenia; Trilaciclib; Life Sciences & Biomedicine; Chemotherapy; INFECTION; Science & Technology; 2ND-LINE TREATMENT; Anemia; Small cell lung cancer; CHEMOTHERAPY-INDUCED NEUTROPENIA; Medicine, Research & Experimental; Patient-reported outcomes; Myelosuppression; Myelopreservation
• Research Categories: Health Sciences, Pharmacology; Chemistry, Radiation; Health Sciences, Oncology

Abstract

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/m2 or placebo before topotecan 1.5 mg/m2 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