No Overall Advantage to Adding Pertuzumab to Chemotherapy in Platinum-Resistant Ovarian Cancer, but Subgroup May Benefit
According to the European phase III PENELOPE trial reported in the Journal of Clinical Oncology, Kurzeder et al found that adding pertuzumab (Perjeta) to investigator’s choice of chemotherapy did not improve progression-free survival in women with low-HER3 mRNA–expressing platinum-resistant ovarian cancer. However, the findings suggested a possible benefit when pertuzumab was added to gemcitabine or paclitaxel.
Study Details
In the double-blind trial, 156 patients with platinum-resistant disease and up to two prior lines of chemotherapy from 52 European sites were randomly assigned between October 2013 and September 2014 to receive investigator’s choice of chemotherapy with single-agent topotecan, weekly paclitaxel, or gemcitabine plus placebo (n = 78) or pertuzumab (n = 78) given at an 840-mg loading dose followed by 420 mg every 3 weeks. Low tumor HER3 mRNA expression was defined as a concentration ratio ≤ 2.81.
In the pertuzumab and placebo groups, 25 and 24 patients received topotecan, 26 and 28 received paclitaxel, and 27 and 26 received gemcitabine. The primary endpoint was progression-free survival assessed by independent review committee.
Key Outcomes
Median duration of follow-up was approximately 10 months. Median progression-free survival was 4.3 months in the pertuzumab group vs 2.6 months in the placebo group (stratified hazard ratio [HR] = 0.74, P = .14). In a subgroup analysis, hazard ratios for progression-free survival favored pertuzumab among patients receiving gemcitabine (4.3 vs 2.1 months, HR = 0.63, 95% confidence interval [CI] = 0.34–1.14) and those receiving paclitaxel (6.4 vs 4.2 months, HR = 0.56, 95% CI = 0.29–1.09) but not among those receiving topotecan (2.8 vs 2.7 months, HR = 1.19, 95% CI = 0.63–2.25). However, the treatment-by-chemotherapy interaction was not significant (P = .16).
Overall response rates for pertuzumab vs placebo were 5.3% vs 0% in patients receiving gemcitabine, 30.0% vs 24.0% in those receiving paclitaxel, and 4.5% vs 0% in those receiving topotecan.
Adverse Events
The most common adverse events of any grade were diarrhea, fatigue/asthenia, nausea, neutropenia, and anemia in the pertuzumab group and fatigue/asthenia, nausea, and anemia in the placebo group. Adverse events of grade ≥ 3 occurred in 69% vs 75%. No new safety signals for pertuzumab treatment were observed.
The investigators concluded: “Although the primary objective was not met, subgroup analyses showed trends in [progression-free survival] favoring pertuzumab in the gemcitabine and paclitaxel cohorts, meriting further exploration of pertuzumab in ovarian cancer.”
The study was supported by F. Hoffmann-La Roche, Basel, Switzerland.
Christian Kurzeder, MD, of Kliniken Essen-Mitte, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
