Compared with other treatments, aldoxorubicin was associated with significantly increased disease control rates (DCR) and prolonged PFS among L-sarcoma (leiomyosarcoma and liposarcoma) participants, reported principal investigator Sant Chawla, MD, director of the Sarcoma Oncology Center in Santa Monica, California.
The intention-to-treat [ITT] 6-month PFS was 24.8% for aldoxorubicin vs 14.9% for other treatments; for L-sarcomas, the 6-month PFS rates were 30.8% vs 14.3%, respectively.
Being treated in North America was also associated with longer PFS rates than were found in western or eastern Europe, Dr Chawla noted. The reasons for this discrepancy are not known.
Overall survival (OS) benefits were, however, not found (median OS: 12.9 with aldoxorubicin vs 12.2 months with other treatments; P = .856).
“Aldoxorubicin, given at 350 mg/m2 per cycle, has minimal to no cardiotoxicity for up to 40 cycles, compared to doxorubicin,” Dr Chawla said. “The non-cardiac grade 3 to 4 adverse events of aldoxorubicin were similar to those of doxorubicin despite exposure to 3 to 4 times the doxorubicin dose.”
LVEF change from baseline was 3.8% among patients administered aldoxorubicin vs 8.5% among patients administered doxorubicin, Dr Chawla said. The proportion of patients with LVEF below 50% at any point after baseline was 4.2% in the aldoxorubicin group compared with 19.1% among patients administered doxorubicin.
Adverse events (AEs) affected almost all patients — 98% in both study arms.
AEs deemed treatment-related were, however, higher in the aldoxorubicin group (94.4% vs 84.1% for any grade; 64.3% vs 46.9% for grade 3 or higher).
Serious treatment-related side effects were also higher in the aldoxorubicin group (28.6% vs 14.5%), although AE-related treatment discontinuation rates were comparable, affecting 10% of patients in both study groups.
Taken together, the phase 3 study’s safety and efficacy findings suggest that aldoxorubicin “may be a superior anthracycline for treating advanced soft tissue sarcoma,” Dr Chawla concluded.
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The team also reported a small, 27-patient study at the ASCO meeting, suggesting that aldoxorubicin can be safely administered with 14 days of continuous ifosfamide and mensa infusion, a regimen that was associated with a 42% partial response rate and a 58% stable disease rate.8
Dr Chawla disclosed conflicts of interests including a consultancy with CytRx, the company that developed aldoxorubicin.
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- Chawla SP, Papai Z, Mukhametshina G, et al. First-line aldoxorubicin vs doxorubicin in metastatic or locally advanced unresectable soft tissue sarcoma: a phase 2b randomized clinical trial. JAMA Oncol. 2015;1(9):1272-80.
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