NEW YORKAt follow-up of more than 2 years, the largest study ever conducted in patients with advanced melanoma has continued to show a trend toward improved survival and a near-doubling of both progression-free survival (PFS) and durable response rates when the targeted antisense drug oblimersen sodium (G3139, Genasense) was added to standard therapy with the alkylating agent dacarbazine (DTIC).
A highly significant survival benefit was seen among patients with normal-range levels of lactate dehydrogenase (LDH) who received the oblimersen/DTIC combination vs DTIC alone, and a continuous relationship emerged between LDH levels and survival outcome. The survival benefit persisted at 3 years or longer follow-up among patients with normal-range LDH.
In an update on use of oblimersen in melanoma, at the Chemotherapy Foundation Symposium XXIV, Sanjiv S. Agarwala, MD, commented on the clinical value of the LDH findings in identifying patients most likely to benefit from an oblimersen/DTIC regimen.
Dr. Agarwala, chief, Medical Oncology Division, St. Luke's Medical Center, Bethlehem, Pennsylvania, presented results of a randomized multinational phase III trial, GM301, by the Oblimersen Study Group. Two-year follow-up results of the study were published recently in the Journal of Clinical Oncology (24:4738-4745, 2006).
The investigators randomly assigned 771 chemotherapy-naive patients with stage IV or unresectable stage III melanoma to treatment with DTIC alone (at 1,000 mg/m2) or DTIC preceded by a 5-day continuous infusion of oblimersen (at 7 mg/kg daily intravenously) every 21 days for up to eight cycles. No cross-over was permitted.
Addition of oblimersen to DTIC yielded a trend toward improved overall survival (OS) at 24-month minimum follow-up (median, 9.0 months vs 7.8 months with DTIC alone, P = .077) as well as significant increases in PFS (median, 2.6 months vs 1.6 months, respectively, P < .001); overall response (13.5% vs 7.5%, P = .007); complete response (2.8% vs 0.8%, P = .031); and durable response (partial response or better lasting at least 6 months; 7.3% vs 3.6%, P = .027).
The incidences of neutropenia and thrombocytopenia were increased in the oblimersen/DTIC group, but there was no increase in the incidences of serious infections or bleeding events. The majority of adverse events in both groups consisted of flulike symptoms.
Impact of LDH