“To date, single-agent programmed cell death 1 protein 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint blockade has shown limited activity in recurrent epithelial ovarian cancer,” wrote the researchers, whose study appeared in JAMA Oncology. “Combination strategies of PD-1/PD-L1 inhibition with antiangiogenic therapy have the potential for synergistic activity through modulation of the microenvironment and represent a potential therapeutic opportunity in this disease.”
The trial was a single-arm, phase 2 study. Women with relapsed epithelial ovarian cancer were enrolled between Feb. 8, 2017, and Dec. 29, 2017, at two U.S.-based sites. Final analysis included 38 patients, all of whom had disease recurrence within 12 months of their most recent platinum-based therapy and had been given between one and three lines of previous therapy. The patients received intravenous nivolumab and intravenous bevacizumab once every two weeks. The main outcome measure was objective response rate (ORR) per the Response Evaluation Criteria in Solid Tumors 1.1. Other outcomes included ORR evaluation by platinum sensitivity, progression-free survival, safety outcomes, and the association of tumor PD-L1 with response to therapy.
The mean (SD) age among the 38 patients was 63.0 (9.1) years; 18 patients had platinum-resistant and 20 had platinum-sensitive disease. Overall, 11 patients experienced a confirmed response to the combination treatment therapy (ORR, 28.9%; 95% exact binomial CI, 15.4%-45.9%); one additional response was unconfirmed. ORR varied between platinum-sensitive (40.0%) and platinum-resistant (16.7%) patients. Most (89.5%) patients sustained at least one treatment-related adverse event (AE), and nine (23.7%) patients experienced a treatment-related AE grade 3 or higher. Among the total cohort, median progression-free survival was 8.1 months. There were 36 histologic samples available for PD-L1 testing, of which 22 (61.1%) samples had a PD-L1 tumoral percentage less than 1, and 14 (38.9%) samples had a PD-L1 tumoral percentage of 1 or greater. Among patients with PD-L1 tumoral percentage less than 1, there were 10 responses, compared to responses in two patients among the PD-L1 tumoral percentage of 1 or greater group.
“The nivolumab with bevacizumab combination appeared to show activity in patients with relapsed ovarian cancer, with greater activity in the platinum-sensitive setting,” the authors summarized. “Alternative combinational strategies may be necessary in the platinum-resistant setting.”