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


METHODS
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' Affiliations: Celestino Hernández Robau Hospital, Villa Clara;
Sailyn
S
Alfonso
Center of Molecular Immunology;
Anet
A
Valdés-Zayas
José R. López Tabranes Hospital, Matanzas;
Eduardo R
ER
Santiesteban
National Institute of Oncology and Radiobiology; and.
Yoanna I
YI
Flores
National Institute of Oncology and Radiobiology; and.
Fernando
F
Areces
Center of Molecular Immunology;
Maurenis
M
Hernández
Center of Molecular Immunology;
Carmen E
CE
Viada
National Coordinating Center of Clinical Trials.
Ivis C
IC
Mendoza
National Coordinating Center of Clinical Trials.
Pedro P
PP
Guerra
National Coordinating Center of Clinical Trials.
Elena
E
García
Authors' Affiliations: Celestino Hernández Robau Hospital, Villa Clara;
Ramón A
RA
Ortiz
Authors' Affiliations: Celestino Hernández Robau Hospital, Villa Clara;
Ana V
AV
de la Torre
Authors' Affiliations: Celestino Hernández Robau Hospital, Villa Clara;
Meylán
M
Cepeda
Center of Molecular Immunology;
Kirenia
K
Pérez
Center of Molecular Immunology;
Eric
E
Chong
Center of Molecular Immunology;
Ana María
AM
Hernández
Center of Molecular Immunology;
Darien
D
Toledo
Center of Molecular Immunology;
Zuyén
Z
González
Center of Molecular Immunology;
Zaima
Z
Mazorra
Center of Molecular Immunology;
Tania
T
Crombet
Center of Molecular Immunology;
Rolando
R
Pérez
Center of Molecular Immunology;
Ana María
AM
Vázquez
Center of Molecular Immunology; amparo@cim.sld.cu.
Amparo E
AE
Macías
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000534:Alum Compounds / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D019496:Cancer Vaccines / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D005679:G(M3) Ganglioside / Q000031:analogs & derivatives / Q000276:immunology / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010919:Placebos; D016016:Proportional Hazards Models; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D019496:Cancer Vaccines; D005679:G(M3) Ganglioside; D010919:Placebos; C041524:aluminum sulfate; C000590234:racotumomab; C044298:N-glycolylneuraminyllactosylceramide