Long-term survival results of a randomized multinational phase 3 trial of dacarbazine (DTIC) with or without Bcl-2 antisense (oblimersen sodium) in patients (pts) with advanced malignant melanoma (MM).

7506 Background: Chemotherapy resistance of MM has been linked to anti-apoptotic proteins, including Bcl-2 that is over-expressed in > 80% of pts. Oblimersen sodium (Genasense; G) targets bcl-2 mRNA and increases apoptosis when added to chemotherapy. We conducted a randomized trial of DTIC (D) alone compared with D plus G in pts with advanced MM. The results of this study, reported after all pts had been enrolled for a minimum of 6 mos, indicated a non-statistically significant difference (P=0.18) in overall survival (OS) for the intent-to-treat population (ITT). (Millward et al, JCO 2004; 22: 14S (abstract 7505)). However, there was a statistically significant difference in landmark analysis at 15 and 18 mos. We report here the update of OS 21 mos after completion of enrollment, as well as follow-up status of pts achieving a complete remission (CR) (11 on G/D vs 2 on D).,771 pts randomized to either G/D or D alone were followed every 2 mos for a total of 24 mos post-randomization. Data were collected and analyzed on survival status after pts had the opportunity to be followed for at least 24 mos post-enrollment. Additional information was collected with regard to disease status in CR patients.,Intent-to-treat (ITT) analysis for all 771 randomized pts shows that the 24 month OS after a minimum of 21 mos of follow-up achieves a significance on log-rank analysis of P=.082. Landmark survival analysis demonstrates significant differences at 15 and 18 mos, and a trend toward significance at 21 mos (p = .036, .012 and .057, respectively). On the G/D arm, 7 of 11 CR pts remain alive and disease-free (survival of 38+, 36+, 36+, 27+, 27+, 27+, 26+ mos). Four pts had progressed with 2 deaths (1 with brain mets only). Survival for these four pts is 23+, 22, 19 and 14+ mos. In the D arm, 1 CR pt remains alive and disease free at 27+ mos; the second pt died of progressive disease at 20 mos.,Genasense enhances the antitumor effectiveness of DTIC, and results in durable CRs in some patients. Follow-up analysis of OS after 24 mos of follow-up, as well as the status of pts with CR will be presented. [Table: see text].