Novel Combination Shows Promise in Recurrent Ovarian Cancer

A combination of pembrolizumab with bevacizumab and cyclophosphamide showed clinical activity and tolerability in patients with recurrent ovarian cancer, a small study found.

Pembrolizumab with bevacizumab and metronomic cyclophosphamide showed clinical activity and had a tolerable toxicity profile in patients with recurrent ovarian cancer, reported a study published in JAMA Oncology.1

The phase 2, single-arm, nonrandomized trial aimed to determine whether the effects of immune checkpoint inhibitors would be improved by the addition of combination bevacizumab and cyclophosphamide therapy in recurrent ovarian cancer treatment. The study population is one with an unmet need, as current treatment options have limited clinical benefit and are detrimental to quality of life.

"Currently, bevacizumab and oral cyclophosphamide is an NCCN-approved regimen and commercially available to treat ovarian cancer patients," said study author Emese Zsiros, a staff physician and faculty member with the Department of Gynecologic Oncology and Center for Immunotherapy at Roswell Park Comprehensive Cancer Center in Buffalo, New York, in an email to Reuters Health.2 "However, with the dual combination, the response rates are not as high and durable."

The trial comprised 40 patients at Roswell Park Comprehensive Cancer Center with platinum-sensitive or platinum-resistant recurrent ovarian cancer who received IV pembrolizumab (200 mg) with bevacizumab (15 mg/kg) every 3 weeks and oral cyclophosphamide (50 mg) daily. Patients who had measurable disease based on immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) and Eastern Cooperative Oncology Group performance status of 0 to 1 were recruited between September 2016 and June 2018.

Primary end points were overall response rate (ORR) and progression-free survival (PFS). Of the patients enrolled, 30 had platinum-resistant and 10 had platinum-sensitive ovarian cancer. Over the course of treatment, 3 patients (7.5%) had complete responses, 16 (40%) had partial responses, and 19 (47.5%) had stable disease in response to treatment based on irRECIST criteria. Median PFS was 10 months (90% CI, 6.5-17.4), and ORR was 47.5%.

The most common grade 3 to 4 treatment-related adverse events were hypertension and lymphopenia (15% and 7.5%, respectively). Fatigue, diarrhea, and hypertension were the most frequently reported adverse events (45%, 32.5%, and 27.5%, respectively).

Overall, the combination regimen showed clinical activity in 95% of the patients enrolled, and 25% had durable responses lasting longer than 12 months. The study authors concluded that it could be a future treatment strategy for recurrent ovarian cancer given its tolerability and the clinical outcomes so far.

Although pembrolizumab is not FDA-approved for recurrent ovarian cancer due to its low response rate when used as a monotherapy, Zsiros’ clinic was able to add it to the approved combination regimen after applying for compassionate drug use, which allows physicians to use investigational drugs in clinical settings under certain criteria.

"We have been using this regimen frequently ever since our trial finished accruing, as we believe this regimen can be very effective and comes with an excellent quality of life compared to traditional second-line chemotherapy drugs," Zsiros said.


1. Zsiros E, Lynam S, Attwood K, et al. Efficacy and Safety of Pembrolizumab in Combination With Bevacizumab and Oral Metronomic Cyclophosphamide in the Treatment of Recurrent Ovarian Cancer. JAMA Oncol. Published online November 19, 2020. Accessed December 11, 2020. doi: 10.1001/jamaoncol.2020.5945

2. Larkin M. Pembrolizumab Plus Bevacizumab and Oral Cyclophosphamide Beneficial in Recurrent Ovarian Cancer. Medscape. December 3, 2020. Accessed December 11, 2020.