Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Study.
Anemia
Chemotherapy
Myelopreservation
Myelosuppression
Neutropenia
Patient-reported outcomes
Small cell lung cancer
Topotecan
Trilaciclib
Journal
Advances in therapy
ISSN: 1865-8652
Titre abrégé: Adv Ther
Pays: United States
ID NLM: 8611864
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
08
09
2020
accepted:
14
10
2020
pubmed:
31
10
2020
medline:
15
4
2021
entrez:
30
10
2020
Statut:
ppublish
Résumé
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). 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 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. 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. ClinicalTrials.gov: NCT02514447.
Identifiants
pubmed: 33123968
doi: 10.1007/s12325-020-01538-0
pii: 10.1007/s12325-020-01538-0
pmc: PMC7854399
doi:
Substances chimiques
Pyrimidines
0
Pyrroles
0
Topotecan
7M7YKX2N15
trilaciclib
U6072DO9XG
Banques de données
ClinicalTrials.gov
['NCT02514447']
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
350-365Références
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