San Diego, CA—Induction therapy with a liposomal formulation of cytarabine and daunorubicin CPX-351 (Vyxeos) is superior to cytarabine plus daunorubicin (7+3 regimen) in patients with acute myeloid leukemia (AML), according to a subgroup analysis of a large phase 3 clinical trial that was presented at the 2016 American Society of Hematology (ASH) meeting.
Lead investigator Jeffrey E. Lancet, MD, Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, presented data from a subgroup analysis of a study presented before ASH. In this clinical trial, CPX-351 prolonged survival in older patients (aged 60-75 years) with high-risk AML who underwent allogeneic hematopoietic cell transplantation (HCT).
The results of the full study were presented earlier and were based on data from 309 patients who were randomized to induction therapy with CPX-351 or to the 7+3 regimen.
The median overall survival (OS) was 9.56 months with CPX-351 versus 5.95 months with the 7+3 regimen, a significant (P = .005) 31% improvement in OS favoring CPX-351. The event-free survival and 60-day mortality also favored CPX-351. No difference was observed between the 2 treatment arms in the frequency and severity of adverse events.
“CPX-351 should become the standard of care for older patients with secondary AML,” said Dr Lancet.
Subgroup Analysis in High-Risk Patients After Transplant
Dr Lancet presented the subgroup analysis of patients in this phase 3 clinical trial who underwent allogeneic HCT.
“The subgroup analysis of the original trial showed that CPX-351 achieves improved survival in high-risk AML in older patients undergoing transplant. The findings suggest that CPX-351 may provide a bridge to transplant and may provide a better opportunity for disease control prior to transplant in this group of patients,” Dr Lancet said. “We plan to study this further,” he added.
The subgroup analysis included 91 patients who underwent allogeneic HCT—52 patients from the CPX-351 treatment group and 39 patients from the 7+3 treatment group. Patients were well-matched for baseline and demographic factors, with the exception of a higher percentage of patients aged ≥70 years in the CPX-351 group than in the 7+3 group (16 vs 6 patients, respectively).
Patients who received CPX-351 were more likely to undergo transplantation, which was performed while the disease was in remission, compared with patients who received the 7+3 regimen. In the entire study, more patients achieved complete response or complete response with incomplete platelet recovery in the CPX-351 group (47.7%) than in the 7+3 group (33.3%).
A landmark analysis of survival from the time of transplant showed that the median OS was not reached in the CPX-351 arm versus 10.25 months in the 7+3 arm, representing a 53% improvement in survival favoring CPX-351 (P = .0046). There were 5 deaths in the CPX-351 arm in the first 100 days after transplant compared with 8 deaths in the 7+3 arm.
“Even though bone marrow transplant can induce significant mortality, death rates were lower in the CPX-351 arm,” Dr Lancet said.