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.

The Added Value of SPECT/CT in Sentinel Lymph Nodes Mapping for Endometrial Carcinoma.

OBJECTIVES: This study was designed to evaluate the detection rate (DR) and sensitivity of sentinel lymph node (SLN) mapping in patients with endometrial cancer using TC99m colloid and blue dye and to evaluate the contribution of preoperative planar lymphoscintigraphy (PLSG) and SPECT/CT. METHODS: A retrospective analysis of patients who underwent SLN mapping as part of their primary surgery for endometrial cancer. Patients underwent preoperative PLSG and later with additional SPECT/CT. Intraoperative detection was performed using TC99m colloid and blue dye by cervical injections. SLNs were sent separately for pathologic evaluation with ultrastaging. RESULTS: Fifty-three patients were included in this study. Successful preoperative mapping was achieved in 31 of 37 patients (84 %) who underwent SPECT/CT compared with only 30 of 45 patients (67 %) who underwent PLSG. SPECT/CT localizations of SLNs were anatomically accurate in 91 % of cases. Intraoperative DR of at least one SLN was 77 %, whilst the bilateral DR was 49 %. DR was significantly better using combined blue dye and TC99m colloid injections compared with blue dye alone: 81 versus 57 % for unilateral and 54 versus 28 % for bilateral mapping (P = 0.01, 0.009, respectively). Six cases of nodal metastasis were diagnosed: four by positive SLNs, and two cases were diagnosed using side-specific full dissection according to the SLN algorithm when SLN detection failed. There were no cases of false-negative results. CONCLUSIONS: SLN detection using cervical injections of TC99m colloid and blue dye is feasible and sensitive for patients with endometrial cancer. SPECT/CT aids to accurate locating of the SLN.