Authors:
L. Yu, A. L. Gilman, M. F. Ozkaynak, W. B. London, S. Kreissman, H. X. Chen, K. K. Matthay, S. L. Cohn, J. M. Maris, & P. Sondel
Summary:
Background - Anti-GD2 monoclonal antibody ch14.18 has shown preclinical and early phase clinical activity against neuroblastoma (NB), with enhanced preclinical efficacy when combined with GM-CSF or IL2. ANBL0032 is a Phase 3 study designed to determine if adding ch14.18 + GM-CSF + IL2 to standard therapy of 13-cis-retinioic acid (RA) given in CR or VGPR after intensive induction and consolidation improved outcome for high-risk NB patients.
Methods - Newly diagnosed high-risk NB patients who achieved a CR or PR to induction therapy and received myeloablative consolidation with stem cell rescue were randomized to RA x 6 cycles (standard) or RA x 6 with 5 concomitant cycles of ch14.18 combined with GM-CSF or IL2 in alternating cycles (ImmRx). Interim monitoring of event-free survival (EFS) was per Lan-Demets with an a*t2 spending function for cumulative a of 0.025. An intent-to-treat randomized comparison was performed using a 1-sided log rank test for EFS and overall survival (OS).
Results - As of 01/12/09, 226 eligible patients were randomized: 113 to standard therapy and 113 to ImmRx. Standard therapy was well tolerated while ImmRx was associated with grade =3 pain (21% of 670 cycles); vascular leak syndrome (7.3%); and allergic reactions (7.2%). With median follow-up of 2.1 yrs after randomization, EFS was significantly higher for patients randomized to ImmRx (p=0.0115), with 2-yr estimates of 66%±5% vs 46%±5% (83 events observed; 61% of expected information). Preliminary OS was also significantly higher for ImmRx (p=0.0223; 86%±4% vs 75%±5% at 2 yrs). The interim monitoring boundary for large early benefit of ImmRx was met and randomization stopped.
Conclusion - Chimeric anti-GD2 antibody ch14.18 combined with GM-CSF and IL2 improves EFS for high-risk NBL patients.
Source:
2009 American Society of Clinical Oncology Annual Meeting; 10067z, Journal of Clinical Oncology; 27, 15s (2009)