Randomized phase 3 trial of interferon gamma-1b plus standard carboplatin/paclitaxel versus carboplatin/paclitaxel alone for first-line treatment of advanced ovarian and primary peritoneal carcinomas: results from a prospectively designed analysis of progression-free survival.

Interferon gamma (IFN-gamma) is a pleiotropic cytokine with antiproliferative, immunostimulatory, and chemosensitization properties. This trial was designed to evaluate IFN-gamma 1b plus carboplatin and paclitaxel in treatment-naive ovarian cancer (OC) and primary peritoneal carcinoma (PPC) patients. Eligible patients were randomized to 6 cycles of carboplatin/paclitaxel every 3 weeks or the same in combination with IFN-gamma 1b (100 microg 3x/wk subcutaneously). The primary endpoint was overall survival (OS) time (target hazard ratio (HR)=0.77). Secondary endpoints included progression-free survival (target HR=0.7), based on blinded review of serial imaging scans, physical exams, and CA-125 levels. 847 patients were enrolled (OC 774, PPC 73) in Europe (n=539) and North/South America (n=308) from January 29, 2002 to March 31, 2004 and stratified according to: optimal debulking (n=271) versus suboptimal debulking with plans for interval debulking (PID) (n=238) or no PID (n=338). The study stopped early following a protocol-defined second interim analysis which revealed significantly shorter OS time in patients receiving IFN-gamma 1b plus chemotherapy compared to chemotherapy alone (1138 days vs. not estimable, HR=1.45, 95% CI=1.15-1.83). At the time of the analysis, 169 of 426 (39.7%) patients in the IFN-gamma 1b plus chemotherapy group had died compared to 128 of 421 (30.4%) in the chemotherapy alone group. Serious adverse events were more common in the IFN-gamma 1b plus chemotherapy group (48.5% vs. 35.4%), primarily due to a higher incidence of serious hematological toxicities (34.5% vs. 22.7%). Treatment with IFN-gamma 1b in combination with carboplatin/paclitaxel does not have a role in the first-line treatment of advanced ovarian cancer.