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.; Hilpert, F.; Martin, A.G.; Rau, J.; Ottevanger, P.; Greimel, E.; ... ; PENELOPE Trial Investigators (2019)

Article / Letter to editor

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 -> 420mg 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.

• HER3
• ovarian cancer
• overall survival
• patient-reported outcomes
• pertuzumab

• All authors: Lorusso, D.; Hilpert, F.; Martin, A.G.; Rau, J.; Ottevanger, P.; Greimel, E.; Luck, H.J.; Selle, F.; Colombo, N.; Kroep, J.R.; Mirza, M.R.; Berger, R.; Pardo, B.; Grischke, E.M.; Berton-Rigaud, D.; Martinez-Garcia, J.; Vergote, I.; Redondo, A.; Cardona, A.; Bastiere-Truchot, L.; Bois, A. du; Kurzeder, C.; Campo, J.M. del; Bover, I.; Barretina-Ginesta, P.; Ortega, E.; Garcia, Y.; Romero, I.; Poveda, A.; Herrero, A.; Vidal, L.; Rubio, M.J.; Romeo, M.; Mendiola, C.; Arranz, J.A.; Santaballa, A.; Liano, A.G. de; Marme, F.; Mahner, S.; Canzler, U.; Zorr, A.; Gropp-Meier, M.; Cayir, P.; Schmalfeldt, B.; Rautenberg, B.; Meier, W.; Belau, A.; Gerber, B.; Rein, D.; Jackisch, C.; Janni, W.; Heubner, M.; Pautier, P.; Fabbro, M.; Floquet, A.; You, B.; Favier, L.; Joly, F.; Weber, B.; Hardy-Bessard, A.C.; Gadducci, A.; Tognon, G.; DeCensi, A.; Savarese, A.; Pisano, C.; Sonke, G.; Reyners, A.; Kristensen, G.; Bjurberg, M.; Rosenberg, P.; Marth, C.; PENELOPE Trial Investigators
• Date: 2019-09-01
• Journal: International Journal of Gynecological Cancer
• Volume: 29
• Issue: 7
• Pages: 1141 - 1147
• DOI: doi:10.1136/ijgc-2019-000370