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CPX-351 improves survival for older patients with high-risk secondary AML
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CHICAGO — CPX-351 prolonged OS and EFS in patients with high-risk secondary acute myeloid leukemia, according to phase 3 study results presented at the ASCO Annual Meeting.
Further, CPX-351 (Vyxeos, Celator) did not increase 60-day mortality or the frequency and severity of adverse events in this population.
Jeffrey E. Lancet
“CPX-351 showed efficacy in phase 1 and phase 2 trials. In this phase 3 trial, CPX-351 showed improved OS and EFS for older patients with secondary AML who were fit for treatment,” Jeffrey E. Lancet, MD, a hematologist at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida said during a presentation. “The ability to deliver the drug as a synergistic, maintained ratio is beneficial, but at this point we do not know the exact underlying cause.”
CPX-351 is a liposomal formulation of cytarabine and daunorubicin (5:1) that has shown efficacy in poor-risk patients with AML.
Because older patients with secondary AML have poor outcomes following first-line cytarabine and anthracycline-based treatment, researchers sought to evaluate the safety and efficacy of first-line CPX-351 for these patients compared with the “7 + 3” standard-of-care chemotherapy regimen.
The analysis included data from 309 patients aged 60 to 75 years with untreated AML who had prior cytotoxic treatment history, antecedent myelodysplastic syndrome or chronic myeloid leukemia, or AML with WHO–defined myelodysplastic syndrome-related cytogenetic abnormalities.
Researchers randomly assigned patients to receive CPX-351 (n = 153; 1,000 units/m2 on days 1, 3 and 5) or 7 + 3 chemotherapy (n = 156; 100 mg/m2 cytarabine daily for 7 days with 60 mg/m2 of daunorubicin on days 1-3). The study arms were balanced for gender, sex, age, race, performance status, AML subtype, cytogenetics and prior hypomethylating therapy.
OS served as the primary endpoint. Other outcome measures included EFS, complete remission and complete remission with incomplete blood count recovery, and 60-day mortality rate.
The study assumed a control median OS of 192 days and analysis after 263 deaths to detect an HR of 0.63 at 93.7% power.
The final analysis occurred after a minimum follow-up of 13.7 months.
Median OS was 9.56 months in the CPX-351 arm compared with 5.95 months in the 7 + 3 arm. These data equated to a significant reduction in mortality with CPX-351 (HR = 0.69; P = 0.005).
Patients in the CPX-351 arm also experienced prolonged EFS (HR = 0.74, P = 0.021). More patients assigned CPX-351 achieved complete remission or complete remission with incomplete blood count recovery (47.7% vs. 33.3%; P = 0.016).
Rates of 60-day mortality were lower in the CPX-351 arm (13.7% vs. 21.2%).
The occurrence of grade 3 to grade 5 adverse events was comparable in both arms (92% vs. 91%).
“This trial treated a population who does not have historically good outcomes,” Richard A. Larson, MD, professor of medicine in the department of hematologic malignancies at University of Chicago, said during the discussion portion of the session. “I do think these data will be sufficient for FDA approval and after approval, [CPX-351] should be considered front-line therapy for this specific subset of patients who are fit for treatment.” – by Nick Andrews
References:
Lancet JE, et al. Abstract 7000. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
Disclos ure: Lancet reports consultant/advisory roles with Amgen, Asterias Biotherapeutics, Baxalta, Boehringer Ingelheim, Celator, Celgene, KaloBios, Karyopharm Therapeutics, Novartis and Shire, as well as research funding paid to his institution from Celgene and Pfizer. Please see the abstract for a list of all other researchers' relevant financial disclosures. Larson reports consultant/advisory roles with Amgen, ARIAD, Bristol-Myers Squibb, Celgene, CVS/Caremark and Novartis and research funding paid to his institution from Amgen, Astellas Pharma, Celgene, Daiichi Sankyo and ERYTECH Pharma.
Perspective
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Noelle Frey, MD, MSCE
The treatment of older patients with acute myeloid leukemia is very challenging because the intensity of treatment is such that many patients cannot endure it. Also, response rates tend to be lower even if patients can tolerate aggressive chemotherapy because the biology of secondary AML tends to be resistant to chemotherapy. This agent was better tolerated and had a lower 60-day mortality rate than the standard arm. Unlike other therapies, where increased response rates may lead to increased toxicity, this study shows that CPX-351 (Vyxeos, Celator) not only improves survival but is better tolerated than the current standard of care (7 + 3 chemotherapy). For the population of patients with AML represented in this study, I think the results are significant enough that when the full scope of the data is reviewed, CPX-351 should be considered as upfront care for this patient population.
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