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Pertuzumab Plus Chemotherapy for Platinum-Resistant Ovarian Cancer: Safety Run-in Results of the PENELOPE Trial
  1. Antonio González-Martín, MD,
  2. Patricia Pautier, MD,
  3. Sven Mahner, MD,
  4. Joern Rau, MSc,
  5. Nicoletta Colombo, MD,
  6. Petronella Ottevanger, MD,
  7. Josep M. del Campo, MD,
  8. Frédéric Selle, MD,
  9. Andreas du Bois, MD,
  10. Angiolo Gadducci, MD,
  11. Yolanda García, MD,
  12. Dominique Berton-Rigaud, MD,
  13. Frederik Marmé, MD,
  14. Eugenia Ortega, MD,
  15. Nicolas Martin, MSc,
  16. Lydie Bastiere-Truchot, PhD,
  17. Astrid Kiermaier, PhD and
  18. Christian Kurzeder, MD
  1. * and Medical Oncology Department, MD Anderson Cancer Center, Madrid, Spain;
  2. GINECO and Medical Oncology Department, Institut Gustave Roussy, Villejuif, France;
  3. AGO and Department of Gynaecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;
  4. § Coordinating Center for Clinical Trials, Philipps-University of Marburg, Marburg, Germany;
  5. MaNGO and Division of Medical Gynecologic Oncology, European Institute of Oncology and University of Milan-Bicocca, Milan, Italy;
  6. DGOG and Department of MedicalOncology, Radboud University Medical Center, Nijmegen, The Netherlands;
  7. # GEICO and Department of Medical Oncology, Vall d’Hebron University Hospital, Barcelona, Spain;
  8. ** GINECO and Tenon Hospital AP-HP and Alliance Pour la Recherche en Cancérologie, France;
  9. †† AGO and Department of Gynecology and GynecologicOncology, Kliniken Essen Mitte, Evang. Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany;
  10. ‡‡ MaNGO and Department of Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy;
  11. §§ GEICO and Medical Oncology Department, Parc Taulí Sabadell-Hospital Universitari, Sabadell, Spain;
  12. ∥∥ GINECO and Medical Oncology Department, Integrated Center for Oncology Nantes-Angers, Nantes, France;
  13. ¶¶ AGO and National Centre for Tumour Diseases, Division of Gynaecologic Oncology, University Hospital Heidelberg, Heidelberg, Germany;
  14. ## GEICO and Department of Medical Oncology, Hospital Universitari Arnau de Vilanova, Lleida, Spain;
  15. *** Global Medical Affairs Biometrics, and
  16. ††† Global Medical Affairs, F. Hoffmann-La Roche Ltd; and
  17. ‡‡‡ Oncology Biomarker Development at Genentech Early Research and Development, Basel, Switzerland.
  1. Address correspondence and reprint requests to Antonio González-Martín, MD, Medical Oncology Department, MD Anderson Cancer Center, C/Arturo Soria 270, 28033 Madrid, Spain. E-mail: agonzalezm{at}


Objective In platinum-resistant ovarian cancer, adding pertuzumab to gemcitabine improved progression-free survival in the subgroup with low tumor HER3 messenger RNA expression. The 2-part PENELOPE trial (NCT01684878) is prospectively investigating pertuzumab plus chemotherapy in this population.

Patients and Methods Part 1 evaluated pertuzumab plus either topotecan or paclitaxel. Patients with platinum-refractory or platinum-resistant recurrent ovarian, primary peritoneal, or fallopian tube cancer and low HER3 messenger RNA expression (concentration ratio ≤2.81 by central quantitative reverse transcriptase-polymerase chain reaction testing on Cobas z480) received intravenous pertuzumab (840 mg loading dose then 420 mg every 3 weeks) with the investigator’s choice of topotecan (1.25 mg/m2 days 1–5 every 3 weeks) or weekly paclitaxel (80 mg/m2) until disease progression or unacceptable toxicity. The primary objective was to assess safety and tolerability.

Results Fifty patients were treated in part 1 (22 topotecan; 28 paclitaxel). In both cohorts, disease progression was the most common primary reason for discontinuing pertuzumab, and the most common all-grade adverse events (AEs) were fatigue/asthenia, anemia, and diarrhea. The most common grade ≥3 AEs were anemia (36%), neutropenia (27%), and fatigue/asthenia (18%) for topotecan, and peripheral sensory neuropathy (14%) and anemia (11%) for paclitaxel. Two patients receiving paclitaxel-pertuzumab died from AEs (abdominal infection; unexplained death). Median progression-free survival was 4.1 months (95% confidence interval, 1.9–6.1) with topotecan-pertuzumab and 4.2 months (95% confidence interval, 3.5–6.0) with paclitaxel-pertuzumab.

Conclusions Based on part 1 tolerability, the Independent Data Monitoring Committee had no objection to PENELOPE proceeding to part 2, a double-blind randomized comparison of chemotherapy (topotecan, paclitaxel, or gemcitabine) plus pertuzumab or placebo.

  • HER3
  • Ovarian cancer
  • Pertuzumab
  • Platinum-resistant
  • Phase 3

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