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Volasertib plus cytarabine extended survival in AML
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The addition of the investigational agent volasertib to low-dose cytarabine improved response and extended survival in patients with acute myeloid leukemia, according to results of a randomized phase 2 trial.
Researchers observed the combination’s activity across AML subgroups, and the regimen also demonstrated a manageable toxicity profile, researchers said.
The analysis included 86 patients (median age, 75 years) with AML who were ineligible for intensive induction therapy. Patients underwent one of two treatment regimens in 4-week cycles.
Hartmut Döhner, MD, of the department of internal medicine at Ulm University in Germany, and colleagues randomly assigned 43 patients to 20 mg cytarabine twice daily for 10 days plus 350 mg volasertib (Boehringer Ingelheim) — a novel polo-like kinase inhibitor — on days 1 and 15. The other 43 patients received volasertib alone.
Objective response, defined as complete remission or complete remission with incomplete blood count recovery, served as the primary endpoint. OS, RFS, and incidence and severity of adverse events served as secondary endpoints.
Döhner and colleagues reported a higher response rate among patients who received volasertib (31% vs. 13.3%; OR=2.91; P=.052). The combination regimen induced responses in patients across all genetic subgroups. Among patients with adverse cytogenics, five of 14 (36%) responded to the combination, and one of 14 (7%) responded to cytarabine alone.
Patients assigned the combination regimen also demonstrated longer median EFS (5.6 months vs. 2.3 months; HR=0.57; 95% CI, 0.35-0.92) and longer median OS (8 months vs. 5.2 months; HR=0.63; 95% CI, 0.4-1).
Döhner and colleagues reported higher rates of grade 3 gastrointestinal events (21% vs. 7%), febrile neutropenia (38% vs. 7%) and infections (38% vs. 7%) in the combination arm. Researchers observed no difference in death rates at 30, 60 or 90 days between treatment groups.
“In recent years, several attempts to improve upon the standard of care in older patients for who intensive induction therapy is not deemed appropriate have failed,” Döhner and colleagues wrote. “A number of novel agents have been tested in single-arm studies, but very few have been validated in randomized, phase 3 trials … In the current trial, the combination of low-dose cytarabine plus volasertib led to response and survival data that appear at least equivalent to data from previous trials conducted in similar patient populations. Based on these encouraging data, a randomized, placebo-controlled, phase 3 trial has been initiated comparing low-dose cytarabine with and without volasertib.”
Disclosure: The researchers report research funding from Boehringer Ingelheim, Novartis and Pfizer, and employment relationships with Boehringer Ingelheim.
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