Double-blind, placebo-controlled, randomized phase III trial evaluating pertuzumab combined with chemotherapy for low tumor human epidermal growth factor receptor 3 mRNA-Expressing platinum-resistant ovarian Cancer (PENELOPE)

Research output: Contribution to journalArticle

Abstract

Purpose The AGO-OVAR 2.29/ENGOT-ov14/PENELOPE prospectively randomized phase III trial evaluated the addition of pertuzumab to chemotherapy in patients with platinum-resistant ovarian carcinoma with low tumor human epidermal growth factor receptor 3 (HER3)mRNA expression. We report the results of the primary efficacy analysis. Patients and Methods Eligible patients had ovarian carcinoma that progressed during or within 6 months of completing four or more platinum cycles, centrally tested low tumor HER3 mRNA expression (concentration ratio # 2.81 by quantitative reverse transcriptase polymerase chain reaction on cobas z480 [Roche Molecular Diagnostics, Pleasanton, CA]), and no more than two prior lines of chemotherapy. After investigators selection of the chemotherapy backbone (single-agent topotecan, weekly paclitaxel, or gemcitabine), patientswere randomly assigned to also receive either placebo or pertuzumab (840-mg loading dose followed by 420 mg every 3 weeks). Stratification factors were selected chemotherapy, prior antiangiogenic therapy, and platinum-free interval. The primary end point was independent review committee-assessed progression-free survival (PFS). Additional end points included overall survival, investigator-assessed PFS, objective response rate, safety, patient-reported outcomes, and translational research. Results Overall, 156 patientswere randomly assigned. Adding pertuzumab to chemotherapy did not significantly improve independent review committee-assessed PFS for the primary analysis (stratified hazard ratio, 0.74; 95% CI, 0.50 to 1.11; P = .14; median PFS, 4.3 months for pertuzumab plus chemotherapy v 2.6 months for placebo plus chemotherapy). Sensitivity analyses and secondary efficacy end point results were consistent with the primary analysis. The effect on PFS favoring pertuzumab was more pronounced in the gemcitabine and paclitaxel cohorts. No new safety signals were seen. Conclusion Although the primary objective was not met, subgroup analyses showed trends in PFS favoring pertuzumab in the gemcitabine and paclitaxel cohorts, meriting further exploration of pertuzumab in ovarian cancer.

Details

Authors
  • Christian Kurzeder
  • Isabel Bover
  • Frederik Marḿe
  • Joern Rau
  • Patricia Pautier
  • Nicoletta Colombo
  • Domenica Lorusso
  • Petronella Ottevanger
  • Maria Bjurberg
  • Christian Marth
  • Pilar Barretina-Ginesta
  • Ignace Vergote
  • Anne Floquet
  • Josep M Del Campo
  • Sven Mahner
  • Lydie Bastíere-Truchot
  • Nicolas Martin
  • Mikkel Z. Oestergaard
  • Astrid Kiermaier
  • Carmen Schade-Brittinger
  • And 3 others
  • Sandra Polleis
  • Andreas Du Bois
  • Antonio Gonzalez-Martin
Organisations
External organisations
  • Kliniken Essen-Mitte
  • Hospital Son Llàtzer
  • University Hospital Heidelberg
  • Philipp University of Marburg
  • Institut Gustave Roussy
  • European Institute of Oncology
  • Istituto Nazionale dei Tumori
  • Radboud Institute for Health Sciences
  • Nordic Society of Gynecological Oncology
  • Medical University of Innsbruck
  • Catalan Institute of Oncology
  • University Hospitals Leuven
  • Institut Bergoníe
  • Vall d'Hebron University Hospital
  • University Medical Center Hamburg-Eppendorf
  • F. Hoffmann-La Roche AG
  • Arbeitsgemeinschaft Gynäkologische Onkologie
  • GEICO
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)2516-25
Number of pages10
JournalJournal of Clinical Oncology
Volume34
Issue number21
Publication statusPublished - 2016 Jul 20
Publication categoryResearch
Peer-reviewedYes