Adding Seribantumab to Paclitaxel Fails to Improve PFS in Advanced Ovarian Cancer
Adding seribantumab, an immunoglobulin G2 monoclonal antibody that binds to HER3, to paclitaxel did not improve progression-free survival.
Adding seribantumab, an immunoglobulin G2 monoclonal antibody that binds to HER3 (ErbB3), to paclitaxel did not improve progression-free survival compared with paclitaxel alone among unselected patients with advanced platinum-resistant or -refractory ovarian cancer, according to a study published in the Journal of Clinical Oncology.1
Preclinical data suggested that blocking heregulin (HRG)/ErbB3 may increase sensitivity to therapy when the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is active. Because seribantumab targets ErbB3 thereby blocking HRG from binding and downregulating the receptor, researchers evaluated the the efficacy and safety of seribantumab plus paclitaxel among patients with advanced ovarian cancer.
For the open-label, phase 2 study (ClinicalTrials.gov Identifier: NCT01447706), investigators enrolled 223 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer resistant or refractory to platinum-based therapy. Participants were randomly assigned 2:1 to receive seribantumab plus paclitaxel or paclitaxel alone.
Median progression-free survival in the unselected intent-to-treat population was 3.75 months with seribantumab plus paclitaxel compared with 3.68 months with paclitaxel alone (hazard ratio [HR], 1.027; 95% CI, 0.741-1.425; P = .864), suggesting no significant difference in progression-free survival between the 2 arms.
Among the 57 patients whose tumors had detectable HRG mRNA and low HER2, the researchers observed a significant reduction in the risk of progression or death with seribantumab vs paclitaxel alone (HR, 0.37; 95% CI, 0.18-0.76; P = .007). In contrast, those who did not meet these criteria had a higher risk of progression or death (HR, 1.80; 95% CI, 1.08-2.98; P = .023).
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Although the study did not meet its primary endpoint of improved progression-free survival with the addition of seribantumab to paclitaxel, exploratory analyses demonstrated that patients with detectable HRG and low HER2 may particularly benefit from this combination. Further studies are warranted to validate this finding in this subpopulation of patients with advanced ovarian cancer.