A randomized, multicenter, placebo-controlled clinical trial of racotumomab-alum vaccine as switch maintenance therapy in advanced non-small cell lung cancer patients.

Abstract

PURPOSE:

Racotumomab-alum is an anti-idiotype vaccine targeting the NeuGcGM3 tumor-associated ganglioside. This clinical trial was conducted to provide a preliminary estimate of efficacy and safety of racotumomab as switch maintenance for patients with advanced non-small cell lung cancer (NSCLC).

EXPERIMENTAL DESIGN:

Patients with stage IIIb/IV NSCLC who have at least stable disease after first-line chemotherapy were randomized 1:1 to racotumomab-alum (5 immunizations every 2 weeks and re-immunizations every 4 weeks) or placebo. Treatment was administered beyond progressive disease, until severe performance status worsening or toxicity. At progression, only five patients per group received further anticancer therapy. The primary endpoint was overall survival (OS).

RESULTS:

One-hundred and seventy-six patients were randomized to racotumomab-alum (n = 87) and placebo (n = 89). Median OS was 8.23 and 6.80 months, respectively [HR, 0.63; 95% confidence interval (CI), 0.46-0.87; P = 0.004]. Median progression-free survival (PFS) in vaccinated patients was 5.33 versus 3.90 months for placebo (HR, 0.73; 95% CI 0.53-0.99; P = 0.039). The most common adverse events in the racotumomab-alum arm were burning and pain at the injection site, bone pain, and asthenia. A high antibody response of IgM and IgG isotype against the NeuGcGM3 ganglioside was obtained. Hyperimmune sera were able to specifically recognize and kill the NeuGcGM3-expressing L1210 cell line. Patients who developed anti-NeuGcGM3 antibodies capable to bind and kill ≥30% L1210 cells showed longer median survival times.

CONCLUSIONS:

Switch maintenance with racotumomab-alum is an effective and a well-tolerated treatment option for patients with advanced NSCLC.

• Authors: Sailyn Alfonso, Anet Valdés-Zayas, Eduardo R Santiesteban, Yoanna I Flores, Fernando Areces, Maurenis Hernández, Carmen E Viada, Ivis C Mendoza, Pedro P Guerra, Elena García, Ramón A Ortiz, Ana V de la Torre, Meylán Cepeda, Kirenia Pérez, Eric Chong, Ana María Hernández, Darien Toledo, Zuyén González, Zaima Mazorra, Tania Crombet, Rolando Pérez, Ana María Vázquez, Amparo E Macías
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 20 Issue 14 Pg. 3660-71 (Jul 15 2014) ISSN: 1557-3265 [Electronic] United States
• PMID: 24788102 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: ©2014 American Association for Cancer Research.

Chemical References

• Adjuvants, Immunologic
• Alum Compounds
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Cancer Vaccines
• G(M3) Ganglioside
• Placebos
• aluminum sulfate
• racotumomab
• N-glycolylneuraminyllactosylceramide

Topics

• Adjuvants, Immunologic (administration & dosage)
• Alum Compounds (administration & dosage)
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Murine-Derived
• Cancer Vaccines (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy, immunology, mortality)
• Double-Blind Method
• Female
• G(M3) Ganglioside (analogs & derivatives, immunology, metabolism)
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms (drug therapy, immunology, mortality)
• Maintenance Chemotherapy
• Male
• Middle Aged
• Neoplasm Staging
• Placebos
• Proportional Hazards Models
• Treatment Outcome