title: Pertuzumab Plus Chemotherapy for Platinum-Resistant Ovarian Cancer: Safety Run-in Results of the PENELOPE Trial.
abstract: 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.
  
  
  
  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/m days 1-5 every 3 weeks) or weekly paclitaxel (80 mg/m) until disease progression or unacceptable toxicity. The primary objective was to assess safety and tolerability.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: * and Medical Oncology Department, MD Anderson Cancer Center, Madrid, Spain; †GINECO and Medical Oncology Department, Institut Gustave Roussy, Villejuif, France; ‡AGO and Department of Gynaecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; §Coordinating Center for Clinical Trials, Philipps-University of Marburg, Marburg, Germany; ∥MaNGO and Division of Medical Gynecologic Oncology, European Institute of Oncology and University of Milan-Bicocca, Milan, Italy; ¶DGOG and Department of MedicalOncology, Radboud University Medical Center, Nijmegen, The Netherlands; #GEICO and Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain; **GINECO and Tenon Hospital AP-HP and Alliance Pour la Recherche en Cancérologie, France; ††AGO and Department of Gynecology and GynecologicOncology, Kliniken Essen Mitte, Evang. Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany; ‡‡MaNGO and Department of Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy; §§GEICO and Medical Oncology Department, Parc Taulí Sabadell-Hospital Universitari, Sabadell, Spain; ∥∥GINECO and Medical Oncology Department, Integrated Center for Oncology Nantes-Angers, Nantes, France; ¶¶AGO and National Centre for Tumour Diseases, Division of Gynaecologic Oncology, University Hospital Heidelberg, Heidelberg, Germany; ##GEICO and Department of Medical Oncology, Hospital Universitari Arnau de Vilanova, Lleida, Spain; ***Global Medical Affairs Biometrics, and †††Global Medical Affairs, F. Hoffmann-La Roche Ltd; and ‡‡‡Oncology Biomarker Development at Genentech Early Research and Development, Basel, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Martín
authors.forename: Patricia
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authors.lastname: Pautier
authors.forename: Sven
authors.initials: S
authors.lastname: Mahner
authors.forename: Joern
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authors.lastname: Rau
authors.forename: Nicoletta
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authors.lastname: Colombo
authors.forename: Petronella
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authors.lastname: Ottevanger
authors.forename: Josep M
authors.initials: JM
authors.lastname: Del Campo
authors.forename: Frédéric
authors.initials: F
authors.lastname: Selle
authors.forename: Andreas
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authors.lastname: du Bois
authors.forename: Angiolo
authors.initials: A
authors.lastname: Gadducci
authors.forename: Yolanda
authors.initials: Y
authors.lastname: García
authors.forename: Dominique
authors.initials: D
authors.lastname: Berton-Rigaud
authors.forename: Frederik
authors.initials: F
authors.lastname: Marmé
authors.forename: Eugenia
authors.initials: E
authors.lastname: Ortega
authors.forename: Nicolas
authors.initials: N
authors.lastname: Martin
authors.forename: Lydie
authors.initials: L
authors.lastname: Bastiere-Truchot
authors.forename: Astrid
authors.initials: A
authors.lastname: Kiermaier
authors.forename: Christian
authors.initials: C
authors.lastname: Kurzeder
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D003841:Deoxycytidine; D019772:Topotecan; C485206:pertuzumab; D017239:Paclitaxel; D000093542:Gemcitabine