Christian Kurzeder1, Isabel Bover2, Frederik Marmé2, Joern Rau2, Patricia Pautier2, Nicoletta Colombo2, Domenica Lorusso2, Petronella Ottevanger2, Maria Bjurberg2, Christian Marth2, Pilar Barretina-Ginesta2, Ignace Vergote2, Anne Floquet2, Josep M Del Campo2, Sven Mahner2, Lydie Bastière-Truchot2, Nicolas Martin2, Mikkel Z Oestergaard2, Astrid Kiermaier2, Carmen Schade-Brittinger2, Sandra Polleis2, Andreas du Bois2, Antonio Gonzalez-Martin2. 1. Christian Kurzeder and Andreas du Bois, Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) and Kliniken Essen Mitte, Essen; Frederik Marmé, AGO and University Hospital Heidelberg, Heidelberg; Joern Rau and Carmen Schade-Brittinger, Coordinating Center for Clinical Trials, Philipps-University of Marburg, Marburg; Sven Mahner, AGO and University Medical Center Hamburg-Eppendorf, Hamburg; Sandra Polleis, AGO Study Group, Wiesbaden, Germany; Isabel Bover, Grupo Español de Investigación en Cáncer de Ovario (GEICO) and Hospital Son Llàtzer, Palma de Mallorca; Pilar Barretina-Ginesta, GEICO and Catalan Institute of Oncology, Girona; Josep M. del Campo, GEICO and Vall d'Hebron University Hospital, Barcelona; Antonio Gonzalez-Martin, GEICO and MD Anderson Cancer Center Spain, Madrid, Spain; Patricia Pautier, Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) and Institut Gustave Roussy, Villejuif; Anne Floquet, GINECO and Institut Bergonié, Bordeaux, France; Nicoletta Colombo, Mario Negri Gynecologic Oncology Group and University of Milan Bicocca-European Institute of Oncology; Domenica Lorusso, Multicenter Italian Trials in Ovarian Cancer and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, National Cancer Institute, Milan, Italy; Petronella Ottevanger, Dutch Gynecological Oncology Group and Radboud University Medical Center, Nijmegen, the Netherlands; Maria Bjurberg, Nordic Society of Gynecological Oncology and Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden; Christian Marth, AGO-Austria and Innsbruck Medical University, Innsbruck, Austria; Ignace Vergote, AGO and University Hospital Leuven, Leuven, Belgium; and Lydie Bastière-Truchot, Nicolas Martin, Mikkel Z. Oestergaard, and Astrid Kiermaier, F. Hoffmann-La Roche, Basel, Switzerland. christian.kurzeder@yahoo.com. 2. Christian Kurzeder and Andreas du Bois, Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) and Kliniken Essen Mitte, Essen; Frederik Marmé, AGO and University Hospital Heidelberg, Heidelberg; Joern Rau and Carmen Schade-Brittinger, Coordinating Center for Clinical Trials, Philipps-University of Marburg, Marburg; Sven Mahner, AGO and University Medical Center Hamburg-Eppendorf, Hamburg; Sandra Polleis, AGO Study Group, Wiesbaden, Germany; Isabel Bover, Grupo Español de Investigación en Cáncer de Ovario (GEICO) and Hospital Son Llàtzer, Palma de Mallorca; Pilar Barretina-Ginesta, GEICO and Catalan Institute of Oncology, Girona; Josep M. del Campo, GEICO and Vall d'Hebron University Hospital, Barcelona; Antonio Gonzalez-Martin, GEICO and MD Anderson Cancer Center Spain, Madrid, Spain; Patricia Pautier, Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) and Institut Gustave Roussy, Villejuif; Anne Floquet, GINECO and Institut Bergonié, Bordeaux, France; Nicoletta Colombo, Mario Negri Gynecologic Oncology Group and University of Milan Bicocca-European Institute of Oncology; Domenica Lorusso, Multicenter Italian Trials in Ovarian Cancer and Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, National Cancer Institute, Milan, Italy; Petronella Ottevanger, Dutch Gynecological Oncology Group and Radboud University Medical Center, Nijmegen, the Netherlands; Maria Bjurberg, Nordic Society of Gynecological Oncology and Department of Clinical Sciences, Skåne University Hospital, Lund University, Lund, Sweden; Christian Marth, AGO-Austria and Innsbruck Medical University, Innsbruck, Austria; Ignace Vergote, AGO and University Hospital Leuven, Leuven, Belgium; and Lydie Bastière-Truchot, Nicolas Martin, Mikkel Z. Oestergaard, and Astrid Kiermaier, F. Hoffmann-La Roche, Basel, Switzerland.
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.
RCT Entities:
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 tumorhuman 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 tumorHER3 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.
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