Randomized-controlled phase II trial of salvage chemotherapy after immunization with a TP53 -transfected dendritic cell-based vaccine (Ad.p53-DC) in patients with recurrent small cell lung cancer

AbstractSmall cell lung cancerTP53 mutations lead to expression of tumor antigens that elicits specific cytotoxic T-cell immune responses. In this phase II study, dendritic cells transfected with wild-typeTP53 (vaccine) were administered to patients with extensive-stage small cell lung cancer after chemotherapy. Patients were randomized 1:1:1 to arm A (observation), arm B (vaccine alone), or arm C (vaccine plus all-trans-retinoic acid). Vaccine was administered every 2 weeks (3 times), and all patients were to receive paclitaxel at progression. Our primary endpoint was overall response rate (ORR) to paclitaxel. The study was not designed to detect overall response rate differences between arms. Of 69 patients enrolled (performance status 0/1, median age 62  years), 55 were treated in stage 1 (18 in arm A, 20 in arm B, and 17 in arm C) and 14 in stage 2 (arm C only), per 2-stage Simon Minimax design. The vaccine was safe, with mostly grade 1/2 toxicities, although 1 arm-B patient experienced grade 3 fatigue and 8 arm-C patients experienced grade 3 tox icities. Positive immune responses were obtained in 20% of arm B (95% confidence interval [CI], 5.3–48.6) and 43.3% of arm C (95% CI 23.9–65.1). The ORRs to the second-line chemotherapy (including paclitaxel) were 15.4% (95% CI 2.7–46.3), 16.7% (95% CI 2.9–49.1), and 23.8% (95% CI 9.1–47.5 ) for arms A, B, and C, with no survival differences between arms. Although our vaccine failed to improve ORRs to the second-line c...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research