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)

Christian Kurzeder, Isabel Bover, Frederik Marme, Joern Rau, Patricia Pautier, Nicoletta Colombo, Domenica Lorusso, P. B. Ottevanger, Maria Bjurberg, Christian Marth, Pilar Barretina-Ginesta, Ignace Vergote, Anne Floquet, Josep M Del Campo, Sven Mahner, Lydie Bastiere-Truchot, Nicolas Martin, Mikkel Z. Oestergaard, Astrid Kiermaier, Carmen Schade-BrittingerSandra Polleis, Andreas du Bois, A. González-Martín

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.

Original languageEnglish
Pages (from-to)2516-2525
Number of pages10
JournalJournal of Clinical Oncology
Volume34
Issue number21
DOIs
Publication statusPublished - Jul 20 2016

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Platinum
Epidermal Growth Factor Receptor
Ovarian Neoplasms
gemcitabine
Disease-Free Survival
Placebos
Drug Therapy
Messenger RNA
Paclitaxel
Neoplasms
Advisory Committees
Research Personnel
Topotecan
Carcinoma
Safety
Translational Medical Research
Molecular Pathology
Survival Analysis
pertuzumab
Reverse Transcriptase Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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). / Kurzeder, Christian; Bover, Isabel; Marme, Frederik; Rau, Joern; Pautier, Patricia; Colombo, Nicoletta; Lorusso, Domenica; Ottevanger, P. B.; Bjurberg, Maria; Marth, Christian; Barretina-Ginesta, Pilar; Vergote, Ignace; Floquet, Anne; Campo, Josep M Del; Mahner, Sven; Bastiere-Truchot, Lydie; Martin, Nicolas; Oestergaard, Mikkel Z.; Kiermaier, Astrid; Schade-Brittinger, Carmen; Polleis, Sandra; Bois, Andreas du; González-Martín, A.

In: Journal of Clinical Oncology, Vol. 34, No. 21, 20.07.2016, p. 2516-2525.

Research output: Contribution to journalArticle

Kurzeder, C, Bover, I, Marme, F, Rau, J, Pautier, P, Colombo, N, Lorusso, D, Ottevanger, PB, Bjurberg, M, Marth, C, Barretina-Ginesta, P, Vergote, I, Floquet, A, Campo, JMD, Mahner, S, Bastiere-Truchot, L, Martin, N, Oestergaard, MZ, Kiermaier, A, Schade-Brittinger, C, Polleis, S, Bois, AD & González-Martín, A 2016, '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)', Journal of Clinical Oncology, vol. 34, no. 21, pp. 2516-2525. https://doi.org/10.1200/JCO.2015.66.0787
Kurzeder, Christian ; Bover, Isabel ; Marme, Frederik ; Rau, Joern ; Pautier, Patricia ; Colombo, Nicoletta ; Lorusso, Domenica ; Ottevanger, P. B. ; Bjurberg, Maria ; Marth, Christian ; Barretina-Ginesta, Pilar ; Vergote, Ignace ; Floquet, Anne ; Campo, Josep M Del ; Mahner, Sven ; Bastiere-Truchot, Lydie ; Martin, Nicolas ; Oestergaard, Mikkel Z. ; Kiermaier, Astrid ; Schade-Brittinger, Carmen ; Polleis, Sandra ; Bois, Andreas du ; González-Martín, A. / 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). In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 21. pp. 2516-2525.
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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.",
author = "Christian Kurzeder and Isabel Bover and Frederik Marme and Joern Rau and Patricia Pautier and Nicoletta Colombo and Domenica Lorusso and Ottevanger, {P. B.} and Maria Bjurberg and Christian Marth and Pilar Barretina-Ginesta and Ignace Vergote and Anne Floquet and Campo, {Josep M Del} and Sven Mahner and Lydie Bastiere-Truchot and Nicolas Martin and Oestergaard, {Mikkel Z.} and Astrid Kiermaier and Carmen Schade-Brittinger and Sandra Polleis and Bois, {Andreas du} and A. Gonz{\'a}lez-Mart{\'i}n",
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T1 - 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)

AU - Kurzeder, Christian

AU - Bover, Isabel

AU - Marme, Frederik

AU - Rau, Joern

AU - Pautier, Patricia

AU - Colombo, Nicoletta

AU - Lorusso, Domenica

AU - Ottevanger, P. B.

AU - Bjurberg, Maria

AU - Marth, Christian

AU - Barretina-Ginesta, Pilar

AU - Vergote, Ignace

AU - Floquet, Anne

AU - Campo, Josep M Del

AU - Mahner, Sven

AU - Bastiere-Truchot, Lydie

AU - Martin, Nicolas

AU - Oestergaard, Mikkel Z.

AU - Kiermaier, Astrid

AU - Schade-Brittinger, Carmen

AU - Polleis, Sandra

AU - Bois, Andreas du

AU - González-Martín, A.

PY - 2016/7/20

Y1 - 2016/7/20

N2 - 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.

AB - 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.

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