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

Objective: Oregovomab is a murine monoclonal antibody directed to the tumor-associated antigen CA125 that stimulates 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, simultaneous day infusion of; oregovomab with paclitaxel and carboplatin dramatically enhanced the magnitude of; induced immunity relative to a 1-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 in optimally resected, stage III/IV ovarian cancer.

Methods: Stage III/IV epithelial ovarian cancer patients optimally debulked to <1 cm residual disease with CA125 >50 U/mL were randomized to carboplatin-paclitaxel + oregovomab; cycle 1,3,5,C5 +12 weeks versus carboplatin-paclitaxel and followed for clinical outcomes and immune response. Secondary endpoints were clinical evaluations and safety.

Results: A total of 97 patients were randomized to the protocol, 47 to carboplatin-paclitaxel-oregovomab and 50 to carboplatin-paclitaxel. Progression-free survival analysis revealed a median progression-free survival of 41.8 months (95% CI 21.8-not estimable [NE]) for carboplatin-paclitaxel-oregovomab and 12.2 months (10.4-18.6) for carboplatin-paclitaxel (HR 0.46, CI 0.28 to 0.7, p = .0027). An updated long-term overall survival analysis was performed with a median follow-up of 109.4 months which demonstrated that in the intent-to treat population the median overall survival for carboplatin-paclitaxel-oregovomab was 121.3 months (95% CI 106.2 to NE) and 64.7 months (95% CI 38.2 to NE) for carboplatin-paclitaxel (HR 0.47, 95% CI 0.26 to 0.86, p = .0116).

Conclusions: This study suggests that simultaneous administration of oregovomab on alternate cycles during front-line carboplatin and paclitaxel could enhance progression-free survival and long-term overall survival. This increase in median overall survival after 9 years of follow-up is meaningful in patients with optimally debulked epithelial ovarian cancer.