Adjunctive Volasertib in Patients With Acute Myeloid Leukemia not Eligible for Standard Induction Therapy: A Randomized, Phase 3 Trial

Autor: Philippe Rousselot, Veronica Teleanu, Kimmo Porkka, Christian Recher, Achilles Anagnostopoulos, Oliver G. Ottmann, Miguel A. Sanz, Daniel J. DeAngelo, Mikkael A. Sekeres, Felicitas Thol, Hartmut Döhner, Kensuke Usuki, Konstanze Döhner, Dries Deeren, Miaomiao Ge, Stefano D'Ardia, Olga Salamero, Irwindeep Sandhu, Chul Won Jung, Tillmann Taube, Je-Hwan Lee, Tomoki Naoe, Koen Theunissen, Jordi Esteve, Heinz-August Horst, Judit Demeter, Walter Fiedler, Valerie Belsack, Argiris Symeonidis, Hee-Je Kim
Přispěvatelé: Institut Català de la Salut, [Döhner H] Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany. [Symeonidis A] Hematology Division, University Hospital, University of Patras Medical School, Patras, Greece. [Deeren D] AZ Delta, Roeselare, Belgium. [Demeter J] Semmelweis University, Budapest, Hungary. [Sanz MA] Department of Hematology, University Hospital La Fe, Valencia, Spain. [Anagnostopoulos A] Hematology Department, General Hospital G. Papanikolaou, Thessaloniki, Greece. [Salamero O] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, HUS Comprehensive Cancer Center, Department of Medicine, Hematologian yksikkö, Helsinki University Hospital Area
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Other subheadings::Other subheadings::/drug therapy [Other subheadings]
Otros calificadores::Otros calificadores::/efectos adversos [Otros calificadores]
Gastroenterology
RECOMMENDATIONS
Persones grans
chemistry.chemical_compound
0302 clinical medicine
DECITABINE
Clinical endpoint
VENETOCLAX
0303 health sciences
Hazard ratio
terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS
DIAGNÓSTICOS Y TERAPÉUTICOS]
Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia
Myeloid::Leukemia
Myeloid
Acute [DISEASES]
Volasertib
Hematology
OPEN-LABEL
3. Good health
030220 oncology & carcinogenesis
Leucèmia mieloide aguda - Quimioteràpia - Complicacions
medicine.drug
medicine.medical_specialty
3122 Cancers
Decitabine
Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores]
KINASE INHIBITOR VOLASERTIB
DIAGNOSIS
Placebo
BI 6727
Article
neoplasias::neoplasias por tipo histológico::leucemia::leucemia mieloide::leucemia mieloide aguda [ENFERMEDADES]
03 medical and health sciences
Internal medicine
Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL
DIAGNOSTIC AND THERAPEUTIC TECHNIQUES
AND EQUIPMENT]
MANAGEMENT
medicine
Other subheadings::Other subheadings::/adverse effects [Other subheadings]
Diseases of the blood and blood-forming organs
Adverse effect
AZACITIDINE
030304 developmental biology
business.industry
medicine.disease
LOW-DOSE CYTARABINE
chemistry
Cytarabine
RC633-647.5
business
Febrile neutropenia
Zdroj: HemaSphere, Vol 5, Iss 8, p e617 (2021)
HemaSphere
Scientia
ISSN: 2572-9241
DOI: 10.1097/HS9.0000000000000617
Popis: Terapia de inducción estándar; Volasertib adyuvante; Leucemia mieloide aguda Standard Induction Therapy; Adjunctive Volasertib; Acute Myeloid Leukemia Teràpia d'inducció estàndard; Volasertib adjuvant; Leucèmia mieloide aguda In this phase 3 trial, older patients with acute myeloid leukemia ineligible for intensive chemotherapy were randomized 2:1 to receive the polo-like kinase inhibitor, volasertib (V; 350 mg intravenous on days 1 and 15 in 4-wk cycles), combined with low-dose cytarabine (LDAC; 20 mg subcutaneous, twice daily, days 1–10; n = 444), or LDAC plus placebo (P; n = 222). Primary endpoint was objective response rate (ORR); key secondary endpoint was overall survival (OS). Primary ORR analysis at recruitment completion included patients randomized ≥5 months beforehand; ORR was 25.2% for V+LDAC and 16.8% for P+LDAC (n = 371; odds ratio 1.66 [95% confidence interval (CI), 0.95–2.89]; P = 0.071). At final analysis (≥574 OS events), median OS was 5.6 months for V+LDAC and 6.5 months for P+LDAC (n = 666; hazard ratio 0.97 [95% CI, 0.8–1.2]; P = 0.757). The most common adverse events (AEs) were infections/infestations (grouped term; V+LDAC, 81.3%; P+LDAC, 63.5%) and febrile neutropenia (V+LDAC, 60.4%; P+LDAC, 29.3%). Fatal AEs occurred in 31.2% with V+LDAC versus 18.0% with P+LDAC, most commonly infections/infestations (V+LDAC, 17.1%; P+LDAC, 6.3%). Lack of OS benefit with V+LDAC versus P+LDAC may reflect increased early mortality with V+LDAC from myelosuppression and infections. This study was funded by Boehringer Ingelheim.
Databáze: OpenAIRE
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