Long-term survival analysis of a randomized phase II study of front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer (QPT-ORE-002).

Abstract

e17592 Background: Oregovomab is a murine monoclonal antibody directed to the tumor-associated antigen CA125 that stimulate host cellular and humoral immune response against tumor cells expressing CA125. A single arm Phase II study in treatment of patients with Epithelial Ovarian Cancer (EOC), simultaneous day infusion of oregovomab with paclitaxel and carboplatin dramatically enhanced the magnitude of induced immunity relative to a one week delayed schedule and other schedules historically evaluated. This randomized Phase II study tested the hypothesis that schedule dependent chemotherapy with oregovomab may improve progression free survival (PFS) in optimally resected, Stage III/IV ovarian cancer. Methods: Stage III/IV EOC patients optimally debulked to <1cm residual disease with CA125 >50u/mL were randomized to CPO (Carboplatin-Paclitaxel + Oregovomab cycle 1,3,5,C5 +12 weeks) vs CP (Carboplatin-Paclitaxel) and followed for clinical outcomes and immune response. Secondary endpoints were clinical evaluations and safety. Results: 97 patients were randomized to the protocol, 47 to CPO and 50 to CP. Previously reported results demonstrated that at a median follow up of 42 months, PFS analysis revealed an unexpectedly large treatment effect for CPO relative to CP alone, with median PFS of 41.8 months (95% C.I.: 21.8 - N.E.) for CPO and 12.2 months (10.4–18.6) for CP (p = 0.0027, HR 0.46, CI 0.28–0.7). The overall survival (OS) OS data was immature at that time, however, the median for CPO had not yet been reached (NE) (45.2-NE) and for CP was 43.2 months (31.8-NE) (p = 0.043, HR 0.35, CI 0.16–0.74). The addition of oregovomab treatment did not result in significant added changes in toxicity profile. An updated long term OS analysis was performed with a median follow up of 109.4 months which demonstrated that in the intent-to treat population the median OS for CPO was 121.3 months (95% CI of 106.2, NE) and 64.7 months (95% CI of 38.2, NE) for CP (p = 0.0116, HR 0.47 - 95% CI of 0.26, 0.86). Conclusions: This study suggests that simultaneous administration of oregovomab on alternate cycles during front-line carboplatin and paclitaxel leverages CP associated temporal change in the tumor microenvironment permitting an immune treatment effect to enhance PFS and long-term OS. This increase in median overall survival after 9 years of follow up is particularly clinically meaningful in patients with optimally debulked EOC. Clinical trial information: NCT01616303 .