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.

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.
Competing Interests: Competing interests: DL has participated in advisory boards for Roche, AstraZeneca, Clovis, Merck and Tesaro; her institution has received research support from Clovis, PharmaMar and Merck. FH has a consultant and advisory relationship with Roche, AstraZeneca and MSD. AGM has consulting and advisory relationships with Roche, Tesaro, AstraZeneca, Pfizer, Clovis, PharmaMar and ImmunoGen. PO has a consulting or advisory role with Novartis, GSK, MSD, Clovis and Tesaro. FS has served as a consultant for Roche and Tesaro. NC has received personal fees from AstraZeneca, Clovis, Tesaro, Roche, PharmaMar, Takeda and Pfizer. BP has participated in advisory boards for Clovis and Tesaro. IV has participated in advisory boards for Advaxis Inc, Eisai Inc, MSD Belgium, Roche NV, Genmab A/S, F. Hoffmann-La Roche Ltd, PharmaMar, Millennium Pharmaceuticals, Clovis Oncology Inc, AstraZeneca NV, Novocure GMBH, Morphotek Inc, Mateon Therapeutics Inc, Immunogen Inc, Eli Lilly Benelux NV, Amgen Inc, Pfizer Inc, Vifor Pharma België NV, Novartis Pharma AG, Oxigene Inc, Nektar Therapeutics and Bayer Pharma AG, has contract research (via K U Leuven) with Oncoinvent AS and Genmab A/S – Genmab B.V., has received grants for corporate-sponsored research from Amgen and Roche, and has received accommodation/travel expenses from Takeda Oncology, PharmaMar, Genmab, Roche and AstraZeneca. AR has consultant and advisory roles with Roche, Tesaro, AstraZeneca, Clovis, PharmaMar, Amgen, Lilly and Novartis, and research funding from Roche, PharmaMar and Eisai. AC and LB-T are employees of and shareholders in Roche. AdB has a consulting and advisory relationship with AstraZeneca, Roche, Tesaro, Pfizer, Clovis, PharMar and Genmab. CK has a consultant and advisory relationships with Roche, AstraZeneca, Tesaro and Genomic Health. All remaining authors have declared no conflicts of interest.
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