Phase II randomized trial of autologous tumor lysate dendritic cell vaccine (ADC) plus best supportive care (BSC) compared with BSC, in pre-treated advanced colorectal cancer patients.

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Journal: J Clin Oncol 33, 2015 (suppl; abstr 3048)
Published: 2015-05-30

Authors:
Joan Maurel, Miguel Caballero-Baños, Jordi Mila, Jaime Tabera, Sara Varea, Ramon Vilana, Luis Bianchi, Pedro Arguis, Estela Pineda, Gemma Carrera, Miriam Cuatrecasas, David Páez, Marta Martin-Richard, Mario Pagés, Juan Ramón Ayuso, Joan Cid, Miguel Lozano, Xabier Garcia-Albeniz, Antoni Castells, Ramon Vilella; Hospital Clinic, Barcelona, Spain; Immunology Department, Hospital Clinic Barcelona, Barcelona, Spain; BST, Sant Boi De Llobregat, Spain; BCLC Group, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain; Hospital Clinic of Barcelona, Barcelona, Spain; Department of Pathology, Hospital Clínic de Barcelona, Barcelona, Spain; Hospital Santa Creu i Sant Pau, Medical Oncology Department, Barcelona, Spain; Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Radiology, Hospital Clínic de Barcelona, Barcelona, Spain; Harvard School of Public Health, Boston, MA; Department of Gastroenterology, Hospital Clínic de Barcelona, Barcelona, Spain

ABSTRACT

Background: No treatments are available for patients (pts) with metastatic colorectal cancer (mCRC) that progresses after all approved therapies. Autologous tumor lysate dendritic cell vaccine (ADC) has T-cell stimulatory capacity and therefore potential antitumor activity. We designed a phase II randomized trial of ADC plus BSC (arm A) compared with BSC (arm B), in pre-treated mCRC patients.

Methods: Pts with documented mCRC and progressive disease at least to two chemotherapy regimens and ECOG performance status (PS) of 0-2, were randomized (1:1 ratio) to arm A vs B. Stratification was done by ECOG PS (0,1 vs 2) and LDH ( < ULN vs > ULN). Arm A was administered subcutaneously days 0,10,20,40,120 and thereafter every 6 months (m) till progressive disease (PD). Radiological evaluation was planned with multidetector computed tomography (MDCT) every 2 m the first 6 m and then every 3 m till PD in both arms. Primary endpoint was progression free rate (PFR) at 4 m. Accordingly, sample size was established in 76 pts to detect differences at month 4 in the PFR of > 30% (40% in the ADC arm and 10% in BSC arm) with an a error = 0.05 and a power = 0.8.

Results: From 08/2011 to 10/2013, 61 pts were screened and 52 pts were included (28 arm A and 24 arm B). An interim analysis recommended early termination for futility. Pts characteristics were well balanced between arms. No ADC-related adverse events were reported. Immunization induces an autologous tumor-specific T-cell response in 21 of 25 (84%) treated pts. Pts with evidence of a vaccine-induced, tumor-specific immune response has a markedly higher overall survival than non-responders (220 days (d) versus 113d); p = 0.026). No objective radiological response was observed in ADC arm. Median PFS and 4 m PFR in arm A was 2.7 m (95%CI 2.3-3.2m) and 15% vs 2.3 m (95%CI 2.1-2.5m) and 21% in arm B (p = 0.628). Median overall survival was 6.2m (95%CI 4.4-7.9m) in arm A vs 4.7m (95%CI 2.3-7m) in arm B (p = 0.41).

Conclusions: Our trial, the first randomized clinical trial comparing ADC plus BSC vs BSC in mCRC, demonstrates that ADC generates a tumor-specific immune response, but not benefit on PFR, PFS and OS compared with BSC. Clinical trial information: NCT01413295

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