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MYELOMA

Survival Rates with Clofarabine Inferior to Standard
Therapy in Older Patients with AML
Despite demonstrating clinical activity in older patients with
newly diagnosed acute myeloid leukemia (AML) in phase II
studies, single-agent clofarabine failed to produce similar
rates of overall survival (OS) to those earlier phase studies in
a phase III trial, when compared with standard therapy.
For more than two decades, newly diagnosed AML patients who are
age 60 or older have been typically treated with induction therapy
with daunorubicin and cytarabine, an intensive treatment regimen
that has been associated with a high incidence of early mortality, lead
author James M. Foran, MD, of the Mayo Clinic Cancer Center in
Jacksonville, Florida, explained. However, given the disappointing
survival rates with clofarabine seen in this trial, the daunorubicin
and cytarabine combination should remain the standard of care.
“We’ve recognized for a long time that there have been limited
advances in survival for older AML patients,” Dr. Foran said. “We’ve
also recognized, through our experience and through national databases, that only a minority – a small minority – of patients actually
gets to the point of receiving potentially curative intensive therapy.”
In this ECOG-ACRIN Cancer Research Group trial, Dr. Foran
and colleagues investigated whether single-agent clofarabine could
potentially lower induction mortality and achieve similar complete remission (CR) rates and OS as standard therapy in older AML patients.
The phase III trial compared the safety and efficacy of clofarabine as induction and consolidation therapy with standard therapy
(daunorubicin and cytarabine) in 727 patients (median age = 68
years; range = 60-86 years). Patients were assigned to receive either:

TABLE 1. Early Treatment Results with Standard Therapy Versus

Clofarabine
Standard therapy
(daunorubicin +
cytarabine)

Clofarabine

CR/CRi

43.8%

42.8%

0.87

30-day mortality

8.5%

7.9%

0.89

60-day mortality

p Value

14.9%

13.1%

0.58

Grade 4-5 non-hematologic toxicity (induction)

27%

19%

0.02

Grade 4-5 nonhematologic toxicity
(consolidation)

20%

7%

0.001

CR=complete remission; CRi=complete remission with incomplete marrow
recovery

inferior OS compared with the standard-therapy group: of the 374
patients who died during the study, 174 were receiving standard
therapy and 200 were receiving clofarabine (hazard ratio [HR] for
OS=1.41 favoring standard therapy; 95% CI 1.12-1.78).
Planned subgroup analyses demonstrated significant differences
in OS favoring standard therapy patients:
• Age 60 to 69 years: HR=1.48 (95% CI 1.99)
• Age ≥70 years: HR=1.34 (95% CI 0.93-1.93)
• Intermediate-risk cytogenetics: HR=1.77 (95% CI 1.27-2.47)

• Clofarabine induction (30 mg/m2 for five days and, if
indicated, 20 mg/m2 for re-induction) followed by two cycles
of consolidation

• Unfavorable-risk cytogenetics: HR=0.96 (95% CI 0.65-1.43)

• Standard therapy: 1-2 cycles of induction (daunorubicin
60 mg/m2 on days 1 through 3 and cytarabine 100 mg/m2 on
days 1 through 7) followed by two cycles of consolidation
with cytarabine (1.5g/m2 every 12 hours on ^\