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
Por:
Caballero-Banos, M, Benitez-Ribas, D, Tabera, J, Varea, S, Vilana, R, Bianchi, L, Ayuso, JR, Pages, M, Carrera, G, Cuatrecasas, M, Martin-Richard, M, Cid, J, Lozano, M, Castells, A, Garcia-Albeniz, X, Maurel, J, Vilella, R
Publicada:
1 sep 2016
Resumen:
Background: 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 and methods: 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 (ULN). EA was administered subcutaneously till progressive disease. Primary end-point was progression-free survival (PFS) at 4 months.
Results: 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).
Conclusion: 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. (C) 2016 Elsevier Ltd. All rights reserved.
Filiaciones:
Caballero-Banos, M:
Hosp Clin Barcelona, Dept Immunol, Barcelona, Spain
Benitez-Ribas, D:
Univ Barcelona, CIBERhed, IDIBAPS, Dept Gastroenterol,Hosp Clin, Barcelona, Spain
Tabera, J:
BST, St Boi De Llobregat, Spain
Varea, S:
Hosp Clin Barcelona, Clin Trials Unit, Barcelona, Spain
Vilana, R:
Univ Barcelona, Hosp Clin, Dept Radiol, BCLC Grp,Liver Unit, Barcelona, Spain
Bianchi, L:
Univ Barcelona, Hosp Clin, Dept Radiol, BCLC Grp,Liver Unit, Barcelona, Spain
Ayuso, JR:
Univ Barcelona, Hosp Clin, Dept Radiol, Barcelona, Spain
Pages, M:
Univ Barcelona, Hosp Clin, Dept Radiol, Barcelona, Spain
Carrera, G:
Hosp Platon, Dept Med Oncol, Barcelona, Spain
Cuatrecasas, M:
Hosp Clin Barcelona, Dept Pathol, Barcelona, Spain
Martin-Richard, M:
Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona, Spain
Cid, J:
Hosp Clin Barcelona, Dept Haemotherapy, Barcelona, Spain
Lozano, M:
Hosp Clin Barcelona, Dept Haemotherapy, Barcelona, Spain
Castells, A:
Univ Barcelona, CIBERhed, IDIBAPS, Dept Gastroenterol,Hosp Clin, Barcelona, Spain
Garcia-Albeniz, X:
Harvard TH Chan Sch Publ Hlth, Boston, MA USA
Maurel, J:
Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain
Vilella, R:
Hosp Clin Barcelona, Dept Immunol, Barcelona, Spain
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