G E Konecny1, A E Wahner Hendrickson2, T M Davidson2, B J Winterhoff3, S Ma4, S Mahner5, J Sehouli6, P A Fasching7, G Feisel-Schwickardi8, M Poelcher9, L D Roman10, A Rody11, B Y Karlan12, S A Mullany3, H Chen13, I L Ray-Coquard14, D M Provencher15, A Yachnin16, P H Cottu17, J A Glaspy13, P Haluska18, D J Slamon13. 1. Division of Hematology/Oncology, University of California Los Angeles, Los Angeles, CA, USA; Division of Gynecologic Oncology, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: gkonecny@mednet.ucla.edu. 2. Division of Oncology Mayo Clinic, Rochester, MN, USA. 3. Department of Obstetrics and Gynecology, University of Minnesota, Minneapolis, MN, USA. 4. Institute for Health Informatics, School of Medicine, University of Minnesota, Minneapolis, MN, USA. 5. Department of Gynecology and Gynecologic Oncology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. 6. University Hospital Charite, Campus Virchow-Klinikum, Klinik für Frauenheilkunde und Geburtshilfe & Nord-Ostdeutsche-Gesellschaft für Gynäkologische Onkologie (NOGGO), Berlin, Germany. 7. Department of Obstetrics and Gynecology, University of Erlangen, Erlangen, Germany. 8. Gynäkologischen Tumorzentrum, Klinikum Kassel, Kassel, Germany. 9. Department of Gynecology, Rotkreutzklinikum, Munich, Germany. 10. USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA. 11. Department of Obstetrics and Gynecology, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Germany. 12. Division of Gynecologic Oncology, University of California Los Angeles, Los Angeles, CA, USA. 13. Division of Hematology/Oncology, University of California Los Angeles, Los Angeles, CA, USA. 14. Centre Léon Bérard, Lyon, France. 15. CHUM - Pavillon Notre-Dame, Montréal, QC, Canada. 16. Department of Oncology, Kaplan Medical Center, Rehovot, Israel. 17. Institut Curie, Paris, France. 18. Bristol-Myers Squibb Inc, Lawrenceville, NJ, USA.
Abstract
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.
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.
Authors: Armel H Nwabo Kamdje; Paul F Seke Etet; Maulilio J Kipanyula; Lorella Vecchio; Richard Tagne Simo; Alfred K Njamnshi; Kiven E Lukong; Patrice N Mimche Journal: Front Endocrinol (Lausanne) Date: 2022-08-09 Impact factor: 6.055