No Advantage to Adding Seribantumab to Paclitaxel in Platinum-Resistant/Refractory Ovarian Cancer, but Subgroup May Benefit

No Advantage to Adding Seribantumab to Paclitaxel in Platinum-Resistant/Refractory Ovarian Cancer, but Subgroup May BenefitIn a phase II study reported in the Journal of Clinical Oncology, Liu et al found no progression-free survival benefit of adding the anti-HER3 (ErbB3) antibody seribantumab to paclitaxel in unselected patients with advanced platinum-resistant or -refractory ovarian cancer. However, exploratory analysis indicated a benefit among women with detectable heregulin mRNA and low HER2 levels. Seribantumab acts to block heregulin-mediated ErbB3 signaling and induce ErbB3 downregulation.

Study Details

In the open-label trial, 223 patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomized 2:1 to receive seribantumab at a 40-mg/kg loading dose and then 20 mg/kg once per week plus paclitaxel given at 80 mg/m2 once per week (n = 140) or paclitaxel alone (n = 83).

Overall and Subgroup Progression-Free Survival

Median progression-free survival in the intent-to-treat population was 3.75 months in the seribantumab/paclitaxel group vs 3.68 months in the paclitaxel group (hazard ratio [HR] = 1.027, P = .864). In an exploratory analysis among 151 patients with biomarker data, median progression-free survival was 5.7 vs 3.5 months (HR = 0.37, P = .007) among the 57 patients with tumors that had detectable heregulin mRNA and low HER2. Outcome was poorer among seribantumab patients without these markers (median progression-free survival = 3.5 vs 5.4 months, HR = 1.80, P = .023).

Adverse Events

Total gastrointestinal adverse events of any grade were more common in the seribantumab group, including diarrhea (73% vs 43%), nausea (43% vs 49%), abdominal pain (29% vs 25%), and vomiting (31% vs 19%). Grade ≥ 3 adverse events occurred in 36% vs 30% of patients, and serious adverse events occurred in 42% vs 31%.

The investigators concluded: “The addition of seribantumab to paclitaxel did not result in improved [progression-free survival] in unselected patients. Exploratory analyses suggest that detectable [heregulin] and low HER2, biomarkers that link directly to the mechanism of action of seribantumab, identified patients who might benefit from this combination. Future clinical trials are needed to validate this finding and should preselect for [heregulin] expression and focus on cancers with low HER2 levels.”

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