Phase IIb Trial Shows Improved Progression-Free Survival With First-Line Aldoxorubicin vs Doxorubicin in Advanced Soft-Tissue Sarcoma


Key Points

  • Aldoxorubicin was associated with improved progression-free survival vs doxorubicin in patients with metastatic or locally advanced soft-tissue sarcoma.
  • No acute cardiotoxicity was observed with aldoxorubicin.

In a randomized phase IIb trial reported in JAMA Oncology, Chawla et al found that aldoxorubicin—a novel albumin-binding prodrug of doxorubicin—produced longer progression-free survival than doxorubicin as first-line treatment for metastatic or locally advanced unresectable soft-tissue sarcoma.

Study Details

In this open-label study, 123 patients from community, private, or institutional practices at 31 sites in Australia, Hungary, India, Romania, Russia, Ukraine, and the United States were randomly assigned 2:1 between August 2012 and December 2013 to receive aldoxorubicin 350 mg/m2 (n = 83; dose equivalent to doxorubicin 260 mg/m2) or doxorubicin 75 mg/m2 (n = 40) every 3 weeks for up to 6 cycles. The primary endpoint was progression-free survival. Overall, patients had a median age of 54.0 years (range = 21–77 years), 34% had leiomyosarcoma, and all had intermediate- to high-grade tumors.

Efficacy Outcomes

On central independent review, median progression-free survival was 5.6 months (95% confidence interval [CI] = 3.0–8.1 months) in the aldoxorubicin group vs 2.7 months (95% CI = 1.6–4.3 months) in the doxorubicin group (P = .02). On investigator assessment, median progression-free survival was 8.3 vs 4.6 months (P < .001). Progression-free survival at 6 months was 46% vs 23% (P = .02) on independent assessment and 68% vs 33% (P < .001) on investigator assessment.

Overall response rates were 25% vs 0% (all partial responses) on independent assessment and 23% (including complete response in 2%) vs 5% on investigator assessment. Median overall survival was 15.8 vs 14.3 months (P = .21).

Adverse Events

Grade 3 or 4 adverse events occurred in 80% of the aldoxorubicin group and 58% of the doxorubicin group. Grade 3 or 4 neutropenia occurred in 29% vs 12%; febrile neutropenia occurred in 14% vs 18%. Treatment was discontinued due to adverse events in 6% vs 8%. No acute cardiotoxic effects were observed in either group. Left ventricular ejection fraction < 50% occurred in no aldoxorubicin patients and in three doxorubicin patients; left ventricular ejection fraction decreases of ≥ 10% were observed in 12% vs 29% of patients.

The investigators concluded: “Single-agent aldoxorubicin therapy showed superior efficacy over doxorubicin by prolonging progression-free survival and improving rates of 6-month progression-free survival and tumor response. Aldoxorubicin therapy exhibited manageable adverse effects, without unexpected events, and without evidence of acute cardiotoxicity. Further investigation of aldoxorubicin therapy in advanced soft-tissue sarcoma is warranted.”

Sant P. Chawla, MD, of Sarcoma Oncology Center, Santa Monica, California, is the corresponding author of the JAMA Oncology article.

This study was funded by CytRx Corporation. For full disclosures of the study authors, visit

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