Pertuzumab Plus Chemotherapy for Platinum-Resistant Ovarian Cancer: Safety Run-in Results of the PENELOPE Trial

Antonio González-Martín, Patricia Pautier, Sven Mahner, Joern Rau, Nicoletta Colombo, Petronella Ottevanger, Josep M. Del Campo, Frédéric Selle, Andreas Du Bois, Angiolo Gadducci, Yolanda García, Dominique Berton-Rigaud, Frederik Marmé, Eugenia Ortega, Nicolas Martin, Lydie Bastiere-Truchot, Astrid Kiermaier, Christian Kurzeder

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)898-905
Number of pages8
JournalInternational Journal of Gynecological Cancer
Volume26
Issue number5
DOIs
Publication statusPublished - Jun 1 2016

Keywords

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

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

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