medwireNews: The doxorubicin conjugate aldoxorubicin could be a suitable alternative to standard therapies for patients with relapsed or refractory soft tissue sarcoma, say researchers.
They suggest this even though the phase III trial comparing aldoxorubicin with investigators’ choice of treatment did not meet its primary endpoint of improved progression-free survival (PFS) with aldoxorubicin.
But aldoxorubicin treatment was associated with less cardiotoxicity than doxorubicin, making it a promising alternative for this patient population, said Sant Chawla (Sarcoma Oncology Center, Santa Monica, California, USA) at the 2017 annual meeting of the American Society of Clinical Oncology, convened in Chicago, Illinois, USA.
Discussant Vinod Ravi, from The MD Anderson Cancer Center in Houston, Texas, USA, agreed, saying that given the “favorable toxicity profile” of aldoxorubicin compared with doxorubicin from the cardiac standpoint, “even if the efficacy is only equivalent between the two drugs, aldoxorubicin still has a significant role as the new-generation anthracycline in our practice.”
Among 433 patients who had relapsed or were refractory to prior chemotherapy, median PFS was comparable between the participants who were randomly assigned to receive aldoxorubicin 350 mg/m2 every 3 weeks and those treated with investigators’ choice of pazopanib, gemcitabine/docetaxel, dacarbazine, doxorubicin, or ifosfamide, at 4.11 and 2.96 months, respectively, and a nonsignificant hazard ratio (HR) of 0.81.
Overall survival also did not differ significantly between trial arms and neither did the objective response rate.
However, a smaller proportion of the 213 aldoxorubicin-treated patients had decreases in left ventricular ejection fraction (LVEF) of at least 20% from baseline at any post-baseline examination than the 47 participants given doxorubicin at the investigators’ discretion, with rates of 3.8% and 8.5%, respectively.
The proportion of patients with an LVEF below 50% at any post-baseline visit was also lower in the aldoxorubicin than doxorubicin group, at 4.2% versus 19.1%, reported Chawla. And the incidence of non-cardiac adverse events of grade 3 or 4 was comparable, “despite exposure to 3–4 times the doxorubicin dose,” he added.
Furthermore, certain subgroups of patients derived a significant PFS benefit from treatment with aldoxorubicin relative to standard therapies. Median PFS was significantly longer with aldoxorubicin among those with leiomyosarcoma or liposarcoma, and in the North American and Australian subgroup, at 5.32 versus 2.96 months (HR=0.62) and 4.21 versus 2.96 months (HR=071), respectively.
On the basis of these findings, the pharmaceutical company is filing for US Food and Drug Administration approval, said Chawla, and he concluded: “If approved, I am hopeful that aldoxorubicin will be the anthracycline of the future, not only in sarcoma but also other solid tumors and malignancies.”
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