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abstract:
Double-Blind, Placebo-Controlled, Randomized Phase III Trial Evaluating Pertuzumab Combined With Chemotherapy for Low Tumor Human Epidermal Growth Factor Receptor 3 mRNA–Expressing Platinum-Resistant Ovarian Cancer (PENELOPE)
June 6, 2016
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.
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.
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