According to the European phase III PENELOPE trial reported in the Journal of Clinical Oncology, Christian Kurzeder, MD, of Kliniken Essen-Mitte, Essen, Germany, et al found that adding pertuzumab (Perjeta) to investigator’s choice 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.
In the double-blind trial, 156 patients with platinum-resistant disease and up to 2 prior lines of chemotherapy from 52 European sites were randomized 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, respectively. The primary endpoint was progression-free survival assessed by independent review committee.
The 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.
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. ■