Nivolumab Plus Bevacizumab Active in Patients With Relapsed Ovarian Cancer

In a phase 2 trial of patients with relapsed epithelial ovarian cancer, combination therapy with nivolumab and bevacizumab led to response rates of 40.0% and 16.7% in patients with platinum-sensitive and platinum-resistant disease (JAMA Oncol. 2019 Oct 10. Epub ahead of print).

“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,” explained Joyce F. Liu, MD, MPH, Division of Gynecologic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues.

Thus, they conducted a single-arm study of 38 patients (mean age, 63.0 years) with relapsed epithelial ovarian cancer to assess the activity of a nivolumab plus bevacizumab therapy regimen in this setting. Of these patients, 18 had platinum-resistant disease and 20 had platinum-sensitive disease.

Patients were enrolled from 2 sites across the United States between February 8, 2017, and December 29, 2017, with primary data analysis completed on July 27, 2018. Patients were eligible for inclusion in the trial if they had been given 1 to 3 previous lines of therapy and had disease recurrence within 12 months of their last platinum-based therapy.

The primary end point of the study was objective response rate (ORR), and secondary end points included ORR by platinum sensitivity, progression-free survival (PFS), safety, and the link between tumor PD-L1 and response to therapy.

There were 11 patients who had confirmed responses to nivolumab plus bevacizumab (ORR, 28.9%; 95% exact binomial CI, 15.4%-45.9%), and 1 additional unconfirmed response. Among patients with platinum-sensitive and platinum-resistant disease, the ORR was 40.0% (95% CI, 19.1%-64.0%) and 16.7% (95% CI, 3.6%-41.4%), respectively.

The occurrence of ≥1 treatment-related adverse events were reported in 34 (89.5%) of patients, and 9 (23.7%) patients had treatment-related adverse events grade ≥3. According to Dr Liu et al, the median PFS rate was 8.1 months (95% CI, 6.3-14.7 months).

PD-L1 testing was able to be performed in 36 histological samples, 22 (61.1%) samples of which had a PD-L1 tumoral percentage <1, and 14 (38.9%) samples of which had a PD-L1 tumoral percentage ≥1. There were 10 and 2 responses reported in patients with PD-L1 tumor percentages <1 and ≥1, respectively.

“The nivolumab with bevacizumab combination appeared to show activity in patients with relapsed ovarian cancer, with greater activity in the platinum-sensitive setting,” Dr Liu and colleagues concluded.

“Alternative combinational strategies may be necessary in the platinum-resistant setting,” they added.—Hina Porcelli