Combination of Bevacizumab With Immune Checkpoint Inhibitor May Have Activity in Relapsed Ovarian Cancer

Immune checkpoint inhibition has revolutionized the treatment of some tumor types, but to date, studies of single-agent immune checkpoint inhibitors in ovarian cancer have shown that these agents have limited activity.

However, researchers have hypothesized that signaling through the vascular endothelial growth factor (VEGF) pathway could have immunomodulatory effects, and a recent study reports on a phase 2 trial that assessed a combination of the immune checkpoint inhibitor nivolumab with the anti-VEGF agent bevacizumab, which now has a commercially available biosimilar.

In the single-arm study, 38 patients (20 of whom had platinum-sensitive disease and 18 of whom had platinum-resistant disease) who had relapsed ovarian cancer with a platinum-free interval of under 12 months received a combination of bevacizumab (10 mg/kg) and nivolumab (240 mg) every 14 days, and treatment continued until disease progression or adverse events (AEs) that led to discontinuation. The primary end point of the study was objective response rate (ORR) using response evaluation criteria in solid tumors (RECIST).

In total, 11 patients had a confirmed response to the combination, for an ORR of 28.9% (95% CI, 15.4%-45.9%). Of the patients with platinum-sensitive disease, there were 8 confirmed responses. Of the patients with platinum-resistant disease, there were 3 confirmed responses. Overall, 27 patients had some degree of tumor decrease.

Among patients who responded, the median duration of response was 6.0 months, and the overall clinical benefit rate was 55.3%. Median progression-free survival, with progression events measured by RECIST, was 9.4 months (95% CI, 6.7 months).

In total, 34 (89.5%) patients had at least 1 treatment-emergent AE, and 9 patients had a grade 3 or higher AE, and 3 grade 4 events were reported. The most commonly reported events were fatigue (47.4%), headache (28.9%), myalgia (28.9%), and serum amylase level increase (28.9%). Four events of pneumonitis and 2 events of colitis were reported.

“The findings suggest that combination therapy with nivolumab and bevacizumab is safe and tolerable in women with relapsed ovarian cancer and may provide evidence of clinical activity,” say the study’s authors, noting that additional study of this potential treatment option is warranted.

Reference

Liu JF, Herold C, Gray KP, et al. Assessment of combined nivolumab and bevacizumab in relapsed ovarian cancer: a phase 2 clinical trial [published online October 10, 2019]. JAMA Oncol. doi:10.1001/jamaoncol.2019.3343.