Final results of phase III SYMMETRY study: randomized, double-blind trial of
elesclomol plus paclitaxel versus paclitaxel alone as treatment for
chemotherapy-naive patients with advanced melanoma.
Author(s): O'Day SJ(1), Eggermont AM, Chiarion-Sileni V, Kefford R, Grob JJ, Mortier L,
Robert C, Schachter J, Testori A, Mackiewicz J, Friedlander P, Garbe C, Ugurel S,
Collichio F, Guo W, Lufkin J, Bahcall S, Vukovic V, Hauschild A.
Affiliation(s): Author information:
(1)Los Angeles Skin Cancer Institute, The Beverly Hills Cancer Center, 8900 Wilshire
Blvd, Beverly Hills, CA 90211, USA. stevenjoday@gmail.com
Publication date & source: 2013, J Clin Oncol. , 31(9):1211-8
PURPOSE: Elesclomol, an investigational first-in-class compound, induces
oxidative stress, triggers mitochondrial-induced apoptosis in cancer cells, and
shows synergy with taxanes in tumor models. Following completion of a phase II
trial of elesclomol in combination with paclitaxel that met its primary end point
of progression-free survival (PFS), this randomized, double-blind, controlled
phase III study was conducted to confirm the efficacy and tolerability of
elesclomol in combination with paclitaxel versus paclitaxel alone in patients
with advanced melanoma.
PATIENTS AND METHODS: Patients with stage IV chemotherapy-naive melanoma (n =
651) were randomly assigned 1:1 to paclitaxel 80 mg/m(2) either alone or in
combination with elesclomol 213 mg/m(2) administered weekly for 3 weeks of a
4-week cycle. Patients were stratified by prior systemic treatment, M1 subclass,
and baseline lactate dehydrogenase (LDH) levels. The primary end point was PFS.
RESULTS: The study did not achieve its PFS end point (hazard ratio, 0.89; P =
.23). The study was stopped when an early overall survival data analysis
indicated an imbalance in total deaths favoring paclitaxel, predominantly in
patients with high LDH levels. A prospectively defined subgroup analysis revealed
a statistically significant improvement in median PFS for the combination in
patients with normal baseline LDH.
CONCLUSION: The addition of elesclomol to paclitaxel did not significantly
improve PFS in unselected patients with advanced melanoma. 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.
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