Summary
Updated data presented at an annual Melanoma conference suggests the drug Elesclomol may benefit a subset of patients treated on a Phase III trial. This Synta Pharmaceuticals-sponsored trial in metastatic melanoma patients was stopped for safety (survival) concerns in February 2009, but the updated analysis suggests that a commonly available biomarker may identify patients who appear to benefit from Elesclomol treatment.
This news is important because it may allow Synta to continue to pursue approval for Elesclomol in either melanoma patients or in other cancers. They will report an updated survival analysis twelve months after the protocol was stopped, after February 2010. Further info from Synta is expected soon.
Analysis
This Phase III trial was based on an earlier randomized Phase II trial combining Elesclomol with paclitaxel compared to paclitaxel alone in the treatment of patients with metastatic cutaneous melanoma. This earlier trial had shown an apparent improvement in progression-free survival (PFS) for the patients receiving both drugs.
The subsequent (similarly designed) randomized double-blind Phase III trial was suddenly stopped by an independent data/safety monitoring board in February 2009 for safety concerns, as analyzed previously.
In October 2009, at the Perspectives XIII Melanoma meeting, the Principal Investigator Dr. Steven O'Day of the Angeles Clinic in Santa Monica, CA, presented data suggesting that patients with low or normal LDH (lactate dehydrogenase) levels appear to have prolonged PFS when treated with both Elesclomol and paclitaxel treatment relative to paclitaxel treatment alone. Survival, still very preliminary in terms of recorded events, was not improved. This PFS improvement was not seen in patients with elevated LDH levels, about 1/3 of the overall treatment group. In fact, preliminary data suggest that patients with elevated LDH levels treated on the combination arm had a worse survival outcome.
Safety data was reported as consistent between the two treatment groups, alleviating potential concerns that the Elesclomol was unacceptably (and unexpectedly) toxic.
LDH is a commonly used biomarker for metastatic cutaneous melanoma patients. Although the mechanism is not understood, patients with elevated LDH levels (defined as above a laboratory's upper limit of normal) have a worse prognosis than patients with normal or reduced LDH levels.
Currently, this prognostic marker is not used to select therapies for metastatic disease, as no approved treatments show differential outcomes based on LDH levels. However, other experimental studies have also shown an association between LDH levels and response to (experimental) therapy for melanoma, including data from Genta's first Phase III Genasense trial.
