ELESCLOMOL FAILED IN MELANOMA 

NEW YORK (Reuters Health) Feb 11 - Elesclomol added to paclitaxel did not improve progression-free survival in patients with advanced melanoma in the phase III SYMMETRY study.

In fact, the study was stopped early after an ad hoc analysis noted an unexplained imbalance in total deaths (80 in the treatment arm and 53 in the control arm).

Elesclomol is a novel investigational drug that exerts anticancer activity by increasing reactive oxygen species, thereby enhancing oxidative stress and apoptosis. It appeared to offer synergistic activity with paclitaxel in earlier studies.

Dr. Steven J. O'Day from The Beverly Hills Cancer Center in California and colleagues tested elesclomol in combination with paclitaxel (vs paclitaxel alone) in a randomized trial of 651 chemotherapy-naive patients with stage IV melanoma.

Patients received one dose per week for three consecutive weeks, followed by one week of rest, in each treatment cycle, as reported online today in the Journal of Clinical Oncology.

At the ad hoc analysis that stopped the trial, there were 80 deaths in the treatment arm and 53 in the control arm.

There was no difference in progression-free survival (PFS), the primary endpoint, between the combination group and the paclitaxel monotherapy group (3.4 vs 1.9 months; p=0.23).

Among patients with normal baseline lactate dehydrogenase (LDH) levels, median PFS was significantly longer for elesclomol-paclitaxel than for paclitaxel-only (3.7 vs 2.1 months; p=0.04), but median PFS did not differ by treatment among patients with elevated baseline LDH levels.

Objective response rates and clinical benefit rates did not differ between the two treatment groups.

Median overall survival did not differ, either, but patients with elevated LDH had a significantly shorter median overall survival with combination treatment than with paclitaxel alone (6.0 vs 7.8 months; p=0.04).

Adverse events occurred with similar frequency in the two treatment groups, although grade 3 or 4 events were more common in the combination group (41% vs 34%).

Of the 16 adverse event-related deaths in the combination group, 12 were attributed to disease progression or were unrelated to elesclomol treatment. All seven adverse event-related deaths in the paclitaxel group were attributed to disease progression.

"In conclusion, the SYMMETRY study did not achieve its primary endpoint," the researchers note. "The association between baseline LDH and clinical outcomes suggests that LDH may be a predictive factor for treatment with this combination, consistent with recent findings on the association between elesclomol anticancer activity and cellular metabolic state."

Synta Pharmaceuticals supported the study and employed 3 of the 19 authors. Two other authors served in consultant or advisory roles for Synta Pharmaceuticals.

Dr. O'Day did not respond to a request for comments on this report.

SOURCE: http://bit.ly/Y5uwUl

J Clin Oncol 2013.