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).

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), patients were 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 patients were 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.

• Authors: Christian Kurzeder, Isabel Bover, Frederik Marmé, 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 Bastière-Truchot, Nicolas Martin, Mikkel Z Oestergaard, Astrid Kiermaier, Carmen Schade-Brittinger, Sandra Polleis, Andreas du Bois, Antonio Gonzalez-Martin
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 34 Issue 21 Pg. 2516-25 (07 20 2016) ISSN: 1527-7755 [Electronic] United States
• PMID: 27269942 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 by American Society of Clinical Oncology.

Chemical References

• Antibodies, Monoclonal, Humanized
• RNA, Messenger
• Carboplatin
• ERBB3 protein, human
• Receptor, ErbB-3
• pertuzumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carboplatin (therapeutic use)
• Double-Blind Method
• Drug Resistance, Neoplasm
• Female
• Humans
• Middle Aged
• Ovarian Neoplasms (drug therapy, mortality)
• RNA, Messenger (analysis)
• Receptor, ErbB-3 (genetics)