TY - JOUR
T1 - 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
AU - PENELOPE trial investigators
AU - Lorusso, Domenica
AU - Hilpert, Felix
AU - González Martin, Antonio
AU - Rau, Joern
AU - Ottevanger, Petronella
AU - Greimel, Elfriede
AU - Lück, Hans Joachim
AU - Selle, Frédéric
AU - Colombo, Nicoletta
AU - Kroep, Judith R.
AU - Mirza, Mansoor R.
AU - Berger, Regina
AU - Pardo, Beatriz
AU - Grischke, Eva Maria
AU - Berton-Rigaud, Dominique
AU - Martinez-Garcia, Jeronimo
AU - Vergote, Ignace
AU - Redondo, Andrés
AU - Cardona, Andrés
AU - Bastière-Truchot, Lydie
AU - Du Bois, Andreas
AU - Kurzeder, Christian
AU - Del Campo, J. M.
AU - Bover, I.
AU - Barretina-Ginesta, P.
AU - Ortega, E.
AU - Garcia, Y.
AU - Romero, I.
AU - Poveda, A.
AU - Herrero, A.
AU - Vidal, L.
AU - Rubio, M. J.
AU - Romeo, M.
AU - Mendiola, C.
AU - Arranz, J. A.
AU - Santaballa, A.
AU - Gomez De Liano, A.
AU - Marme, F.
AU - Mahner, S.
AU - Canzler, U.
AU - Zorr, A.
AU - Gropp-Meier, M.
AU - Cayir, P.
AU - Schmalfeldt, B.
AU - Rautenberg, B.
AU - Meier, W.
AU - Belau, A.
AU - Gerber, B.
AU - Rein, D.
AU - Reyners, A.
N1 - Funding Information:
Funding This work was supported by F. Hoffmann-La Roche, Basel, Switzerland. No grant number applicable. F. Hoffmann-La Roche was involved in the design of the trial in collaboration with the Steering Committee. Authors representing F.
Publisher Copyright:
© IGCS and ESGO 2019. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Introduction: 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.Results: 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.Discussion: 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.
AB - Introduction: 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.Results: 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.Discussion: 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.
KW - HER3
KW - ovarian cancer
KW - overall survival
KW - patient-reported outcomes
KW - pertuzumab
U2 - 10.1136/ijgc-2019-000370
DO - 10.1136/ijgc-2019-000370
M3 - Article
C2 - 31420414
AN - SCOPUS:85070969107
SN - 1048-891X
VL - 29
SP - 1141
EP - 1147
JO - International Journal of Gynecological Cancer
JF - International Journal of Gynecological Cancer
IS - 7
ER -