Zeitschrift für onkologische Forschung und Behandlung

Abstrakt

Final Efficacy Results of a Randomized Phase II Study of Recombinant Interleukin-21 Compared to Dacarbazine in Patients with Recurrent or Metastatic Melanoma

Teresa M. Petrella, Catalin Mihalcioiu, Jose Monzon, Elaine McWhirter, Karl Belanger, Kerry J. Savage, Xinni Song, Omid Hamid, Tina Cheng, Mary Davis, Christopher W. Lee, Alan Spatz, Linda Hagerman, Bingshu E. Chen and Janet Dancey

Objective: Interleukin-21(IL-21) is a T-cell derived cytokine with antitumour activity dependent on NK cells or CD8+ T cells. A previous phase II study demonstrated an overall response rate (ORR) of 22.5% in previously untreated patients with metastatic melanoma. We conducted a multi-centre randomized phase II study in metastatic melanoma patients to evaluate the efficacy, toxicity, immunogenicity and biomarkers associated with response to IL-21 versus dacarbazine (DTIC).

Methods: Eligible patients: Recurrent, non-resectable or metastatic melanoma patients were treated with either IL-21, 30 μg/kg/day dose intravenous (IV) daily x 5 days, weeks 1, 3, 5, q 8 weeks or dacarbazine (DTIC) 1000 mg/ m2 IV day 1, q 3 weeks. The primary objective was to compare progression free survival (PFS).

Results: 64 patients were randomized, 32 in the IL-21 arm and 32 in the DTIC arm. In the treated population, PFS (1.87 months for IL-21, 2.04 months for DTIC) and ORR {IL-21: 13.3% (95% CI: 3.8 to 30.7), DTIC: 14.3% (95% CI: 4.0 to 32.7)} was similar in both groups. Most common adverse events (AEs) in Arm 1 (IL-21) were nausea (38%), fatigue (56%), fever (34%), maculo-papular rash (34%), and pruritis (38%). In Arm 2 (DTIC) the most common AEs were fatigue (39%), constipation (29%), and nausea (21%). Biomarker studies showed no correlation of sCD25 changes and PFS outcome (HR=0.86, 95% CI. 0.73 to 1.02).

Conclusions: Despite encouraging efficacy in prior phase I/II studies, the results suggest that IL-21 is comparable to DTIC in this specific patient population.