Pembrolizumab Plus Bevacizumab and Cyclophosphamide Shows Promising Efficacy, Tolerability in Recurrent Ovarian Cancer
Real-world data from a retrospective study showed that pembrolizumab combined with the anti-VEGF agent bevacizumab plus oral metronomic cyclophosphamide displayed minimal toxicity in a significant number of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal 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.
- 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.
- 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