Effective and safe therapies are critically needed for patients with relapsed or treatment-resistant acute myeloid leukaemia (AML), a disease for which there is currently no standard of care or approved treatments.

The chemotherapy agent cytabarine has been used since the 1960s either alone or in combination with other agents to treat aggressive AML; however these cytarabine-based treatment approaches are associated with substantial adverse effects and are not effective for many patients.

By combining cytabarine with new agents, researchers hope to develop an effective treatment for AML that does not cause significant additional toxicity.

One such agent is vosaroxin, a therapy that can induce cancer cell death by causing site-specific DNA damage.

Researchers have investigated this compound in a Phase III randomised trial 'VALOR' to evaluate its ability to overcome the limitations of current therapies without the cardiotoxicities commonly observed with other treatments.

In the trial, 711 adult AML patients at 124 sites worldwide with relapsed disease or disease unresponsive to other therapies were randomised to receive cytarabine together with either vosaroxin or placebo.

Patients treated with vosaroxin achieved longer overall survival compared to those treated with placebo (7.5 months vs. 6.1 months), but this difference did not achieve statistical significance (p=0.06).

When censoring for transplantation, however, the survival benefit was statistically significant (p= 0.02).

Patients who received vosaroxin were also more likely to achieve complete responses (CR) to the treatment (30.1% experiencing CR in the vosaroxin arm vs. 16.3% in the placebo arm).

Patients 60 or older and those experiencing early relapse experienced the greatest overall survival benefit from the treatment.

Early mortality was similar in the two arms, and the most common adverse events in both groups included neutropenia, sepsis, infection, and mouth sores.

“In this study, one of the largest randomised trials conducted in the setting of relapsed/refractory AML, the combination of vosaroxin and cytarbine demonstrated longer survival time and almost double the complete response rates compared to cytarabine alone. The benefit was particularly visible in older patients, who experienced manageable added toxicity,” said lead study author Farhad Ravandi, MD, of The University of Texas MD Anderson Cancer Center in Houston.

“Although it is clear that we still have a long way to go to improve outcomes for such patients, these data provide support that the vosaroxin/cytarabine combination is the most effective approach to date for treatment of older patients with this challenging condition.”

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Source: ASH