Phase III, randomized, double-blind study of elesclomol and paclitaxel versus paclitaxel alone in stage IV metastatic melanoma (MM): 1-year OS update.

Abstract

8550^ Background: Elesclomol is an investigational first-in-class oxidative stress inducer that increases reactive oxygen species in cancer cells leading to mitochondria-induced apoptosis. Methods: Patients (pts) withstage IV MM, no prior chemotherapy, LDH £ 2x ULN were randomized (1:1) to either 213 mg/m2 elesclomol in combination with 80 mg/m2 paclitaxel (ELPAC) or 80 mg/m2 paclitaxel alone (P). Pts were stratified by prior noncytotoxic treatment, M1 grade, and LDH and received once weekly ELPAC or P for 3 weeks followed by a 1 week's rest until disease progression. PFS was the primary endpoint, and the study was powered for OS analysis. Results: 651 pts were enrolled between September 2007 and February 2009. As previously reported, despite a trend in improvement of PFS, ELPAC failed to demonstrate a statistically significant improvement compared to P (HR=0.88; p value=0.1875). Six-month OS data is presented below. PFS and OS outcome appears to correlate with LDH level. 12-month OS data will be presented at time of meeting. Conclusions: Baseline LDH is emerging as an important predictor of both PFS and OS outcome for treatment with ELPAC. Patients with normal baseline LDH: an improvement in PFS compared to P; no difference in OS observed to date. Patients with elevated baseline LDH: no PFS improvement and a decrease in median survival time compared to P. PFS Six-month OS ELPAC p ELPAC p ITT n = 651 Median (months) 3.4 1.9 10.6 11.3 HR (95% CI) 0.88 (0.73-1.06) 1.17 (0.93-1.48) 55% censored Normal LDH (>1 × ULN) n = 443 Median (months) 3.6 2.1 13.6 13.9 HR (95% CI) 0.76 (0.60-0.97) 0.99 (0.72-1.36) 65% censored Elevated LDH (≥1 × ULN) n = 208 Median (months) 1.8 1.9 5.9 7.9 HR (95% CI) 1.10 (0.81-1.50) 1.49 (1.05-2.11) 34% censored Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Synta Synta Synta Synta Synta In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest.