Pembrolizumab Plus Bevacizumab and Cyclophosphamide Shows Promising Efficacy, Tolerability in Recurrent Ovarian Cancer

Real-world data from a retrospective study showed that pembrolizumab (Keytruda) combined with the anti-VEGF agent bevacizumab (Avastin) plus oral metronomic cyclophosphamide displayed minimal toxicity with long-term clinical responses in a significant number of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.¹ Data were presented in a poster at the ESMO Congress 2022.

Following the completion of a phase 2 clinical trial (NCT02853318) conducted at Roswell Park Comprehensive Cancer Center in Buffalo, New York, investigators used the regimen of pembrolizumab 200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 weeks plus 50 mg daily cyclophosphamide on a 21-day cycle in clinical practice.

Heavily pretreated patients (n = 55) were enrolled in the retrospective, single-center study. These patients had a mean number of 3.4 prior lines of chemotherapy received (range 1-9).

The median overall survival (OS) was 14 months (95% CI, 11-not reached) with a 6-month OS rate of 93.7% and a 12-month rate of 65%. The objective response rate (ORR) was 42%, including 3 patients with a complete response (CR). Slightly less than half (49%) of patients achieved stable disease and the total clinical benefit rate was 91%. The median progression-free survival (PFS) was 7.8 months (95% CI, 4.5-10.3) and the 6-month and 12-month PFS rates of were 61.1% and 24.5%, respectively.

Stable disease at 24 weeks or more was reported in 26% of patients and was 74% at less than 24 weeks. Only 9% of the patients included in the retrospective study experienced disease progression.

Investigators reported that these data also demonstrated improved quality-of-life outcomes.

The mean age of patients in the retrospective study was 63.4 years. Nine patients (17%) were BRCA positive, 11 (20%) were PD-L1 positive, and 32 (58%) had a history of platinum chemotherapy resistance. Prior bevacizumab therapy was reported in 30 (55%) of those in the trial and 3 (6%) had previous cyclophosphamide treatment.

Single-agent immune checkpoint inhibitors are not largely effective in the treatment of recurrent ovarian cancer and because there is limited efficacy with traditional second-line chemotherapies in this patient population, investigators aimed to determine if the combination therapy would have a promising efficacy with ORR and PFS as measurements of the efficacy primary end point.

The combination therapy had a minimal toxicity in the retrospective study. The most common adverse events (AEs) of any grade included fatigue, nausea/vomiting, abdominal pain, and constipation. Fatigue has the highest incidence, reported among over 90% of patients.

Comparatively, in the phase 2 trial, patients in the safety population (n = 40) experienced AEs of any grade and grade 3 or 4 at a rate of 83.5% and 32.5%, respectively.²

The median PFS was 10.0 months (90% CI, 6.5-17.4). The ORR was 47.5%, including a 7.5% CR rate. The clinical benefit rate was 95% with 47.5% of patients having stable disease. The durable response rate was 25%.

The combination of pembrolizumab, bevacizumab, and metronomic cyclophosphamide may be a future treatment for recurrent ovarian cancer, study authors wrote in conclusion.

References

1. Poblete S, Caulkins MA, Roche CL, et al. Pembrolizumab in combination with bevacizumab and oral metronomic cyclophosphamide for recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer—real-life clinical experience. Poster presented at: 2022 European Society for Medical Oncology; September 9-13, 2022; Paris, France.
2. Zsiros E, Lynam S, Attwood KM, et al. Efficacy and safety of pembrolizumab in combination with bevacizumab and oral metronomic cyclophosphamide in the treatment of recurrent ovarian cancer: a phase 2 nonrandomized clinical trial. JAMA Oncol. 2021;7(1):78-85. doi:10.1001/jamaoncol.2020.5945