2区 · 医学
Article
作者: Wimberger, Pauline ; Madry, Radoslaw ; Chovanec, Josef ; Cibula, David ; Galluzzi, Lorenzo ; Minar, Lubos ; Pluta, Marek ; Pecen, Ladislav ; Hassan, Hariz Iskandar Bin ; Kieszko, Dariusz ; Bartos, Pavel ; Fucikova, Jitka ; Klat, Jaroslav ; Markowska, Janina ; Mallmann, Peter ; Bartunkova, Jirina ; Knapp, Pawel ; Melichar, Bohuslav ; Hein, Alexander ; Rob, Lukas ; Streb, Joanna ; Hrnciarova, Tereza ; Hraska, Marek ; Spacek, Jiri ; Spisek, Radek ; Valha, Petr
OBJECTIVE:DCVAC/OvCa is an active cellular immunotherapy designed to stimulate an immune response against ovarian cancer. We explored the safety and efficacy of DCVAC/OvCa plus carboplatin and gemcitabine in platinum-sensitive ovarian cancer.
METHODS:In this open-label, parallel-group, phase 2 trial (ClinicalTrials.gov number NCT02107950), patients with platinum-sensitive ovarian cancer relapsing after first-line chemotherapy were randomized to DCVAC/OvCa and chemotherapy or chemotherapy alone. DCVAC/OvCa was administered every 3-6 weeks (10 doses). Endpoints included safety, progression-free survival (PFS; primary efficacy endpoint) and overall survival (OS; secondary efficacy endpoint).
RESULTS:Between November 2013 and May 2015, 71 patients were randomized to chemotherapy in combination with DCVAC/OvCa or to chemotherapy alone. Treatment-emergent adverse events related to DCVAC/OvCa, leukapheresis and chemotherapy occurred in six (16.2%), two (5.4%), and 35 (94.6%) patients in the DCVAC/OvCa group. Chemotherapy-related events occurred in all patients in the chemotherapy group. Seven patients in the DCVAC/OvCa group were excluded from primary efficacy analyses due to failure to receive ≥1 dose of DCVAC/OvCa. PFS was not improved (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.42-1.28, P = 0.274, data maturity 78.1%). Median OS was significantly prolonged (by 13.4 months) in the DCVAC/OvCa group (HR 0.38, 95% CI 0.20-0.74, P = 0.003; data maturity 56.3%). A signal for enhanced surrogate antigen-specific T-cell activity was seen with DCVAC/OvCa.
CONCLUSIONS:DCVAC/OvCa combined with chemotherapy had a favorable safety profile in patients with platinum-sensitive ovarian cancer. DCVAC/OvCa did not improve PFS, but the exploratory analyses revealed OS prolongation and enhanced surrogate antigen-specific T-cell activity.