title: A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non-Small Cell Lung Cancer Patients.
abstract: EGFR is a well-validated target for patients with non-small cell lung cancer (NSCLC). CIMAvax-EGF is a therapeutic cancer vaccine composed of human recombinant EGF conjugated to a carrier protein and Montanide ISA51 as adjuvant. The vaccine is intended to induce antibodies against self EGFs that block EGF-EGFR interaction.
  
  
  
  To evaluate overall survival, safety, immunogenicity, and EGF concentration in serum after CIMAvax-EGF, a randomized phase III trial was done in patients with advanced NSCLC. Four to 6 weeks after first-line chemotherapy, 405 patients with stage IIIB/IV NSCLC were randomly assigned to a vaccine group, which received CIMAvax-EGF or a control group, treated with best supportive care.
  
  
  
  Long-term vaccination was very safe. Most frequent adverse reactions were grade 1 or 2 injection-site pain, fever, vomiting, and headache. Vaccination induced anti-EGF antibodies and decreased serum EGF concentration. In the safety population, median survival time (MST) was 10.83 months in the vaccine arm versus 8.86 months in the control arm. These differences were not significant according the standard log rank (HR, 0.82; P = 0.100), but according a weighted log rank (P = 0.04) that was applied once the nonproportionality of the HR was verified. Survival benefit was significant (HR, 0.77; P = 0.036) in the per-protocol setting (patients receiving at least four vaccine doses): MST was 12.43 months for the vaccine arm versus 9.43 months for the control arm. MST was higher (14.66 months) for vaccinated patients with high EGF concentration at baseline.
  
  
  
  Switch maintenance with CIMAvax-EGF was well tolerated and significantly increased MST of patients that completed induction vaccination. Baseline EGF concentration predicted survival benefit. Clin Cancer Res; 22(15); 3782-90. ©2016 AACR.
authors.affiliation: Centre for Molecular Immunology, Havana, Cuba. camilo@cim.sld.cu.
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Rodriguez
authors.affiliation: Centre for Molecular Immunology, Havana, Cuba.
authors.forename: Xitllaly
authors.initials: X
authors.lastname: Popa
authors.affiliation: Vladimir I. Lenin University Hospital, Holguín Province, Cuba.
authors.forename: Odeth
authors.initials: O
authors.lastname: Martínez
authors.affiliation: Manuel Ascunce University Hospital, Camagüey Province, Cuba.
authors.forename: Silvia
authors.initials: S
authors.lastname: Mendoza
authors.affiliation: José L. Lopez Tabranes University Hospital, Matanzas Province, Cuba.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Santiesteban
authors.affiliation: Benefico Jurídico Pneumological Hospital, Havana, Cuba.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Crespo
authors.affiliation: III Congreso University Hospital, Pinar del Rio Province, Cuba.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Amador
authors.affiliation: Salvador Allende University Hospital, Havana, Cuba.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fleytas
authors.affiliation: Saturnino Lora University Hospital, Santiago de Cuba Province, Cuba.
authors.forename: Soraida C
authors.initials: SC
authors.lastname: Acosta
authors.affiliation: Camilo Cienfuegos University Hospital, Sancti Spiritus Province, Cuba.
authors.forename: Yanine
authors.initials: Y
authors.lastname: Otero
authors.affiliation: Carlos M. de Céspedes University Hospital, Granma Province, Cuba.
authors.forename: Gala N
authors.initials: GN
authors.lastname: Romero
authors.affiliation: Celestino Hernández University Hospital, Villa Clara Province, Cuba.
authors.forename: Ana
authors.initials: A
authors.lastname: de la Torre
authors.affiliation: Dr. Juan B. Zayas University Hospital, Santiago de Cuba Province, Cuba.
authors.forename: Mireysi
authors.initials: M
authors.lastname: Cala
authors.affiliation: Maria Curie University Hospital, Camagüey Province, Cuba.
authors.forename: Lina
authors.initials: L
authors.lastname: Arzuaga
authors.affiliation: Antonio Luaces University Hospital, Ciego de Ávila Province, Cuba.
authors.forename: Loisel
authors.initials: L
authors.lastname: Vello
authors.affiliation: Ernesto Guevara University Hospital, Tunas Province, Cuba.
authors.forename: Delmairis
authors.initials: D
authors.lastname: Reyes
authors.affiliation: Celia Sánchez University Hospital, Granma Province, Cuba.
authors.forename: Niurka
authors.initials: N
authors.lastname: Futiel
authors.affiliation: Dr. Gustavo Aldegueria University Hospital, Cienfuegos Province, Cuba.
authors.forename: Teresa
authors.initials: T
authors.lastname: Sabates
authors.affiliation: Centre for Medical & Surgical Research, Havana, Cuba.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Catala
authors.affiliation: National Institute for Oncology & Radiobiology, Havana, Cuba.
authors.forename: Yoanna I
authors.initials: YI
authors.lastname: Flores
authors.affiliation: Centre for Molecular Immunology, Havana, Cuba.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Garcia
authors.affiliation: Centre for Molecular Immunology, Havana, Cuba.
authors.forename: Carmen
authors.initials: C
authors.lastname: Viada
authors.affiliation: Centre for Molecular Immunology, Havana, Cuba.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lorenzo-Luaces
authors.affiliation: National Center for Clinical Trials Coordination, Havana, Cuba.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Marrero
authors.affiliation: National Center for Clinical Trials Coordination, Havana, Cuba.
authors.forename: Liuba
authors.initials: L
authors.lastname: Alonso
authors.affiliation: National Center for Clinical Trials Coordination, Havana, Cuba.
authors.forename: Jenelin
authors.initials: J
authors.lastname: Parra
authors.affiliation: National Center for Clinical Trials Coordination, Havana, Cuba.
authors.forename: Nadia
authors.initials: N
authors.lastname: Aguilera
authors.affiliation: Centre for Molecular Immunology, Havana, Cuba.
authors.forename: Yaisel
authors.initials: Y
authors.lastname: Pomares
authors.affiliation: Centre for Molecular Immunology, Havana, Cuba.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sierra
authors.affiliation: Centre for Molecular Immunology, Havana, Cuba.
authors.forename: Gryssell
authors.initials: G
authors.lastname: Rodríguez
authors.affiliation: Centre for Molecular Immunology, Havana, Cuba.
authors.forename: Zaima
authors.initials: Z
authors.lastname: Mazorra
authors.affiliation: Centre for Molecular Immunology, Havana, Cuba.
authors.forename: Agustin
authors.initials: A
authors.lastname: Lage
authors.affiliation: Centre for Molecular Immunology, Havana, Cuba.
authors.forename: Tania
authors.initials: T
authors.lastname: Crombet
authors.affiliation: Hermanos Ameijeiras University Hospital, Havana, Cuba.
authors.forename: Elia
authors.initials: E
authors.lastname: Neninger
mesh_terms: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D004815:Epidermal Growth Factor / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006801:Humans; D016233:Immunotherapy, Active; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D019233:Retreatment; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D004815:Epidermal Growth Factor