title: Phase II randomised trial of autologous tumour lysate dendritic cell plus best supportive care compared with best supportive care in pre-treated advanced colorectal cancer patients.
abstract: Autologous tumour lysate dendritic cell vaccine (ADC) has T-cell stimulatory capacity and, therefore, potential antitumour activity. We designed a phase II randomised trial of ADC + best supportive care (BSC) (experimental arm [EA]) compared with BSC (control arm [CA]), in pre-treated metastatic colorectal cancer (mCRC) patients.
  
  
  
  Patients with progressive mCRC, at least to two chemotherapy regimens and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2, were randomised to EA versus CA. Stratification criteria: ECOG PS (0-1 versus 2) and lactate dehydrogenase (<Upper Limit of Normal [ULN] versus >ULN). EA was administered subcutaneously till progressive disease. Primary end-point was progression-free survival (PFS) at 4 months.
  
  
  
  Fifty-two patients were included (28 EA/24 CA). An interim analysis recommended early termination for futility. No objective radiological response was observed in EA. Median PFS in EA was 2.7 months (95% confidence interval [CI], 2.3-3.2 months) versus 2.3 months (95% CI, 2.1-2.5 months) in CA (p = 0.628). Median overall survival (OS) was 6.2 months (95% CI, 4.4-7.9 months) in EA versus 4.7 months (95% CI, 2.3-7 months) in CA (p = 0.41). No ADC-related adverse events were reported. Immunization induces tumour-specific T-cell response in 21 of 25 (84%) patients. Responder patients have an OS of 7.3 months (95% CI, 5.2-9.4 months) versus 3.8 months (95% CI, 0.6-6.9 months) in non-responders; p = 0.026).
  
  
  
  Our randomised clinical trial comparing ADC + BSC versus BSC in mCRC demonstrates that ADC generates a tumour-specific immune response but not benefit on PFS and OS. Our results do not support the use of ADC alone, in a phase III trial.
authors.affiliation: Department of Immunology, Hospital Clinic, Barcelona, Spain. Electronic address: miguelcaballerobanos@gmail.com.
authors.forename: Miguel
authors.initials: M
authors.lastname: Caballero-Baños
authors.affiliation: Department of Gastroenterology, Hospital Clinic, iDIBAPS, CIBERhed, University of Barcelona, Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Benitez-Ribas
authors.affiliation: BST, Sant Boi De Llobregat, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Tabera
authors.affiliation: Clinical Trials Unit, Hospital Clinic, Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Varea
authors.affiliation: Department of Radiology, BCLC Group, Liver Unit, Hospital Clinic, University of Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Vilana
authors.affiliation: Department of Radiology, BCLC Group, Liver Unit, Hospital Clinic, University of Barcelona, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Bianchi
authors.affiliation: Department of Radiology, Hospital Clinic, University of Barcelona, Spain.
authors.forename: Juan Ramón
authors.initials: JR
authors.lastname: Ayuso
authors.affiliation: Department of Radiology, Hospital Clinic, University of Barcelona, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Pagés
authors.affiliation: Department of Medical Oncology, Hospital Platon, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Carrera
authors.affiliation: Department of Pathology, Hospital Clinic Barcelona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Cuatrecasas
authors.affiliation: Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Martin-Richard
authors.affiliation: Department of Haemotherapy, Hospital Clinic, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Cid
authors.affiliation: Department of Haemotherapy, Hospital Clinic, Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Lozano
authors.affiliation: Department of Gastroenterology, Hospital Clinic, iDIBAPS, CIBERhed, University of Barcelona, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Castells
authors.affiliation: Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Xabier
authors.initials: X
authors.lastname: García-Albéniz
authors.affiliation: Department of Medical Oncology, Hospital Clinic, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Maurel
authors.affiliation: Department of Immunology, Hospital Clinic, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Vilella
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016019:Survival Analysis
chemical_list: D019496:Cancer Vaccines
keywords: Cancer; Colorectal; Dendritic cells; Immunotherapy; Vaccine