Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer
Lorusso D (#1), Hilpert F (#2,3), González Martin A (4,5), Rau J (6), Ottevanger P (7), Greimel E (8), Lück HJ (9), Selle F (10), Colombo N (11), Kroep JR (12), Mirza MR (13), Berger R (14), Pardo B (15), Grischke EM (16), Berton-Rigaud D (17), Martinez-Garcia J (18), Vergote I (19), Redondo A (20), Cardona A (21), Bastière-Truchot L (21), du Bois A (22), Kurzeder C (22,23); PENELOPE trial investigators.
(1) Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
(2) Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) and Klinik für Gynäkologie und Geburtshilfe, Kiel, Germany (affiliation when work was performed).
(3) Mammazentrum am Krankenhaus Jerusalem, Hamburg, Germany.
(4) Grupo Español de Investigación en Cáncer de Ovario (GEICO) and MD Anderson Cancer Center Spain, Madrid, Spain (affiliation when work was performed).
(5) Clínica Universidad de Navarra, Madrid, Spain.
(6) Coordinating Center for Clinical Trials, Philipps-University of Marburg, Marburg, Germany.
(7) Dutch Gynaecological Oncology Group (DGOG) and Department of Medical Oncology, Radboud University Medical Center, Nijmegen, Netherlands.
(8) Medical University Graz, Graz, Austria.
(9) AGO and Gynäkologisch-Onkologische Praxis am Pelikanplatz, Hannover, Germany.
(10) Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), Groupe Hospitalier Diaconesses Croix Saint-Simon and Alliance Pour la Recherche en Cancérologie, Paris, France.
(11) Mario Negri Gynecologic Oncology (MaNGO) group, IEO, European Institute of Oncology IRCCS, and University of Milan-Bicocca, Milan, Italy.
(12) DGOG and Department of Medical Oncology, Leids Universitair Medisch Centrum, Leiden, Netherlands.
(13) Nordic Society of Gynaecological Oncology (NSGO) and Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
(14) AGO-Austria and University Hospital for Gynaecology and Obstetrics, Medical University of Innsbruck, Innsbruck, Austria.
(15) GEICO and Medical Oncology Department, Institut Català d'Oncologia, Hospital Duran i Reynals, Barcelona, Spain.
(16) AGO and University Hospital of Gynecology and Obstetrics, Tübingen, Germany.
(17) GINECO and Integrated Center for Oncology Nantes-Angers, Nantes, France.
(18) GEICO and Medical Oncology Service, Hospital Clínico Universitario Virgen de la Arrixaca, El Palmar, Spain.
(19) AGO and Leuven Cancer Institute, University Hospital Leuven, Leuven, Belgium.
(20) GEICO and Medical Oncology Department, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
(21) F. Hoffmann-La Roche, Basel, Switzerland.
(22) AGO and Kliniken Essen Mitte, Essen, Germany.
(23) Department of Gynecology and Gynecological Oncology, University Hospital Basel, University of Basel, Basel, Switzerland.
The PENELOPE trial evaluated pertuzumab added to chemotherapy for biomarker-selected platinum-resistant ovarian cancer. As previously reported, pertuzumab did not statistically significantly improve progression-free survival (primary end point: HR 0.74, 95% CI 0.50 to 1.11), although results in the paclitaxel and gemcitabine cohorts suggested activity. Here, we report final overall survival and patient-reported outcomes.
PATIENTS AND METHODS:
Eligible patients had ovarian carcinoma that progressed during/within 6 months of completing ≥4 platinum cycles, low tumor human epidermal growth factor receptor 3 (HER3) mRNA expression, and ≤2 prior chemotherapy lines. Investigators selected single-agent topotecan, gemcitabine or weekly paclitaxel before patients were randomized to either placebo or pertuzumab (840→420 mg every 3 weeks), stratified by selected chemotherapy, prior anti-angiogenic therapy, and platinum-free interval. Final overall survival analysis (key secondary end point) was pre-specified after 129 deaths. Patient-reported outcomes (secondary end point) were assessed at baseline and every 9 weeks until disease progression.
At database lock (June 9, 2016), 130 (83%) of 156 randomized patients had died. Median follow-up was 27 months in the pertuzumab arm versus 26 months in the control arm. In the intent-to-treat population there was no overall survival difference between treatment arms (stratified HR 0.90, 95% CI 0.61 to 1.32; p=0.60). Results in subgroups defined by stratification factors indicated heterogeneity similar to previous progression-free survival results. Updated safety was similar to previously published results. Compliance with patient-reported outcomes questionnaire completion was >75% for all validated patient-reported outcomes measures. Pertuzumab demonstrated neither beneficial nor detrimental effects on patient-reported outcomes compared with placebo, except for increased diarrhea symptoms.
Consistent with the primary results, adding pertuzumab to chemotherapy for low tumor HER3 mRNA-expressing platinum-resistant ovarian cancer did not improve overall survival, but showed trends in some cohorts. Except for increased diarrhea symptoms, pertuzumab had no impact on patient-reported outcomes. ClinicalTrials.gov: ClinicalTrials.gov: NCT01684878.
CITATION Int J Gynecol Cancer. 2019 Aug 15. pii: ijgc-2019-000370. doi: 10.1136/ijgc-2019-000370.