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

Konecny GE, Hendrickson AE, Davidson TM, Winterhoff BJ, Ma S, Mahner S, Sehouli J, Fasching P, Feisel-Schwickardi G, Poelcher M, Roman LD, Rody A, Karlan BY, Mullany SA, Chen H, Ray-Coquard IL, Provencher DM, Yachnin A, Cottu PH, Glaspy JA, Haluska P, Slamon DJ (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Gynecologic Oncology Elsevier

DOI: 10.1016/j.ygyno.2021.09.025

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.

Authors with CRIS profile

Peter Fasching Professur für Translationale Frauenheilkunde und Geburtshilfe

Involved external institutions

University of California Los Angeles (UCLA) US United States (USA) (US) Mayo Clinic US United States (USA) (US) University of Minnesota (UMN) US United States (USA) (US) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Klinikum Kassel GmbH DE Germany (DE) Rotkreuzklinikum München DE Germany (DE) Keck School of Medicine of USC US United States (USA) (US) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Centre Léon-Bérard (UNICANCER) FR France (FR) Centre hospitalier de l'Université de Montréal (CHUM) CA Canada (CA) Kaplan Medical Center / מרכז רפואי קפלן IL Israel (IL) Institut Curie FR France (FR) Bristol-Myers Squibb US United States (USA) (US)

How to cite

APA:

Konecny, G.E., Hendrickson, A.E., Davidson, T.M., Winterhoff, B.J., Ma, S., Mahner, S.,... Slamon, D.J. (2021). 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. Gynecologic Oncology. https://doi.org/10.1016/j.ygyno.2021.09.025

MLA:

Konecny, G. E., et al. "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." Gynecologic Oncology (2021).

BibTeX: Download