Results of TRIO-14, a phase II, multicenter, randomized, placebo-controlled trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-ganitumab in newly diagnosed epithelial ovarian cancer.

PURPOSE: Insulin-like growth factor (IGF) signaling is implicated in pathogenesis and chemotherapy resistance of epithelial ovarian cancer (EOC). We explored efficacy and safety of adding ganitumab, a monoclonal antibody targeting IGF-1R, to carboplatin/paclitaxel (CP) chemotherapy in patients with primary EOC. DESIGN: Patients were randomly assigned to receive CP/ganitumab (18 mg/kg q3w) or CP/placebo for 6 cycles followed by 6 cycles of single agent ganitumab/placebo maintenance therapy as front-line therapy. Primary endpoint was progression free survival. Secondary endpoints were time to progression and overall survival. Pretreatment samples were prospectively collected for retrospective biomarker analyses. RESULTS: 170 patients enrolled. 165 patients assessable for toxicity. Median PFS was 15.7 months with CP/ganitumab and 16.7 months with CP/placebo (HR 1.23; 95% CI 0.82-1.83, P = 0.313). All grade neutropenia (84.1% vs 71.4%), thrombocytopenia (75.3% vs 57.1%) and hyperglycemia (15.9% vs 2.6%) were more common in the ganitumab group compared to the placebo group. Ganitumab/placebo related serious adverse events were reported in 26.1% of the patients with ganitumab and in 6.5% with placebo. Non-progression related fatal events were more common with ganitumab (5 versus 2 patients). The ganitumab group experienced more dose delays which resulted in lower relative dose intensity of chemotherapy in the experimental group. In an exploratory model IGFBP2 expression was predictive of ganitumab response (treatment interaction; PFS, P = 0.03; OS, P = 0.01). CONCLUSION: Addition of ganitumab to CP chemotherapy in primary EOC did not improve PFS. Our results do not support further study of ganitumab in unselected EOC patients.

Surgery for recurrent ovarian cancer: role of peritoneal carcinomatosis: exploratory analysis of the DESKTOP I Trial about risk factors, surgical implications, and prognostic value of peritoneal carcinomatosis.

BACKGROUND: Almost all retrospective trials pointed out that a benefit of surgery for recurrent ovarian cancer may be limited to patients in whom a macroscopic complete resection could be achieved. Peritoneal carcinomatosis has been reported to be either a negative predictor for resectability or a negative prognostic factor, or both. The role of peritoneal carcinomatosis in a multicenter trial was investigated. METHODS: Exploratory analysis of the DESKTOP I trial (multicenter trial of patients undergoing surgery for recurrent ovarian cancer, 2000 to 2003). RESULTS: A total of 125 patients (50%) who underwent surgery for recurrent ovarian cancer had peritoneal carcinomatosis. Univariate analyses showed worse overall survival for patients with peritoneal carcinomatosis compared with patients without carcinomatosis (P < .0001). Patients with and without peritoneal carcinomatosis had a complete resection rate of 26% and 74%, respectively (P < .0001). This corresponded with the observation that patients with complete resection had a better prognosis than those with minimal residual disease of 1 to 5 mm, which commonly reflects peritoneal carcinomatosis (P = .0002). However, patients who underwent complete resection, despite peritoneal carcinomatosis, had a 2-year survival rate of 77%, which was similar to the 2-year survival rate of patients with completely debulked disease who did not have peritoneal carcinomatosis (81%) (P = .96). Analysis of prognostic factors did not show any independent effect of peritoneal carcinomatosis on survival in patients who underwent complete resection. CONCLUSIONS: Peritoneal carcinomatosis was a negative predictor for complete resection but had no effect on prognosis if complete resection could be achieved. Improving surgical skills might be one step to increase the proportion of patients who might benefit from surgery for recurrent disease.