Adjunctive Volasertib in Patients With Acute Myeloid Leukemia not Eligible for Standard Induction Therapy: A Randomized, Phase 3 Trial
Hartmut Döhner, Argiris Symeonidis, Dries Deeren, Judit Demeter, Miguel Á. Sanz, Αchilles Anagnostopoulos, Jordi Esteve, Walter Fiedler, Kimmo Porkka, Hee‐Je Kim, Je‐Hwan Lee, Kensuke Usuki, Stefano D’Ardìa, Chul Won Jung, Olga Salamero, Heinz‐August Horst, Christian Récher, Philippe Rousselot, Irwindeep Sandhu, Koen Theunissen, Felicitas Thol, Konstanze Döhner, Veronica Teleanu, Daniel J. DeAngelo, Tomoki Naoe, Mikkael A. Sekeres, Valérie Belsack, Miaomiao Ge, Tillmann Taube, Oliver G. Ottmann
Abstract
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.