The triplet of pembrolizumab plus bevacizumab and oral cyclophosphamide is associated with a disease control rate of 95% and is well-tolerated in women with recurrent ovarian cancer, according to results from a single-arm, open-label, phase 2 nonrandomized trial. The median progression-free survival (PFS) was 10 months.
“In the absence of curative therapy for treatment-refractory disease, the incorporation of target-specific treatments and immunotherapy with meaningful response in ovarian cancer are crucial for women diagnosed with recurrence,” the investigators, led by Emese Zsiros, MD, PhD, from Roswell Park Comprehensive Cancer Center, Buffalo, wrote in JAMA Oncology.
They also noted that, “combining anti–PD-1 and antiangiogenic therapy with metronomic cyclophosphamide represents a novel opportunity to augment cytotoxic lymphocyte function while potentially modulating harmful regulatory T-cell responses and optimizing vascularization within the tumor microenvironment.”
In the single-institution study, 40 women with histologically confirmed recurrent ovarian cancer and measurable disease per immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) received intravenous pembrolizumab 200 mg, and bevacizumab 15 mg/kg, every 3 weeks, and oral cyclophosphamide 50 mg once daily during a 21-day treatment cycle until disease progression, unacceptable toxic effects, or withdrawal of consent.
The mean age of the participants was 62.2 years; 30 (75%) had platinum-resistant ovarian cancer, and 10 (25%) had platinum-sensitive disease. The mean number of lines of prior chemotherapy was 3.4 for the overall cohort and 3.8 for those with platinum-resistant disease. Fourteen (35.0%) patients had prior exposure to bevacizumab and 5 (12.5%) had prior oral cyclophosphamide exposure.
Fourteen (35.0%) patients had germline or somatic BRCA variants, 23 (57.5%) patients had BRCA-negative status (germline and somatic), and 3 (7.5%) had unknown BRCA status.
Three (7.5%) women had a complete response (CR) and 16 (40.0%) had a partial response (PR) per irRECIST, for an objective response rate (ORR) of 47.5%. Another 19 (47.5%) patients had stable disease, for a clinical benefit rate of 95.0%. Median time to best response was 5.8 months.
There were 6 confirmed PRs in patients with platinum-sensitive disease (ORR, 60.0%) compared with 13 PRs and CRs (9 confirmed) in patients with platinum-resistant disease (ORR, 43.3%). Durable responses were achieved in 10 (25.0%) patients.
The 7-month PFS rate was 0.67 (90% confidence interval, 0.53-0.78), the investigators noted, which exceeded the predefined threshold of 0.3 to be considered significant in a heavily pretreated ovarian cancer cohort.
Patients with platinum-sensitive disease had a median PFS of 20.2 months compared with 7.6 months in patients with platinum-resistant disease (P = .16).
Patients who received ≤3 lines of prior chemotherapy before being enrolled had significantly better PFS (10.8 vs 6.5 months; P = .03) and overall survival (26.1 vs 12.5 months; P = .03), compared with patients with ≥3 prior lines of treatment.
The most common grade 3/4 treatment-related adverse events were hypertension (15.0%) and lymphopenia (7.5%). The most frequently reported adverse events of any grade were fatigue (45.0%), diarrhea (32.5%), and hypertension (27.5%).