Pembrolizumab Plus Bevacizumab and Oral Cyclophosphamide Beneficial in Recurrent Ovarian Cancer

By Marilynn Larkin

December 03, 2020

NEW YORK (Reuters Health) - In patients with recurrent ovarian cancer, the combination of pembrolizumab plus bevacizumab and oral cyclophosphamide demonstrated clinical benefit and was well-tolerated in a phase 2 nonrandomized trial.

"We used pembrolizumab to activate T cells; bevacizumab to help T cells to enter tumor tissue; and oral cyclophosphamide to deplete the bad immunosuppressive T-reg immune cells," Dr. Emese Zsiros of Roswell Park Comprehensive Cancer Center in Buffalo in New York told Reuters Health by email. "Overall, this triple therapy regimen was very well tolerated in these women, with three responding completely, 16 responding partially, 22 patients with stable disease, and a disease control rate of 95%."

"Currently, bevacizumab and oral cyclophosphamide is an NCCN-approved regimen and commercially available to treat ovarian cancer patients," he noted. "However, with the dual combination, the response rates are not as high and durable."

"In our clinic, we are able to add pembrolizumab to this regimen as well, through applying for free drug for compassionate use (pembrolizumab is not FDA-approved for recurrent ovarian cancer due to the low response rate as a single agent therapy)," he said. "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."

As reported in JAMA Oncology, of the 40 women enrolled in the trial (mean age, 62), 30 (75%) had platinum-resistant ovarian cancer and 10 (25%), platinum-sensitive. Participants received intravenous pembrolizumab, 200 mg, and bevacizumab, 15mg/kg, every three weeks, and oral cyclophosphamide, 50 mg, once daily during until disease progression, unacceptable toxic effects, or consent withdrawal.

As Dr. Zsiros indicated, three women (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; clinical benefit was seen in 38 (95%), and durable response in 10 (25%).

Overall, the median progression-free survival (PFS) was 10 months. Patients with platinum-sensitive disease had a median PFS of 20.2 months compared with 7.6 months in those with platinum-resistant disease.

The most common grade 3-4 treatment-related adverse events were bevacizumab-induced hypertension (15%) and lymphopenia attributed to cyclophosphamide (7.5%). The most frequently reported adverse events were fatigue (45%), diarrhea (32.5%), and hypertension (27.5%).

Dr. Zsiros said, "Our next step is to analyze all the collected biospecimens in order to understand what made certain patients exceptional, durable responders."

Dr. John Diaz, Deputy Chief of Gynecologic Oncology at Miami Cancer Institute, commented by email to Reuters Health, "The combination of bevacizumab and oral cyclophosphamide is a regimen I use in my practice. The addition of pembrolizumab to this regimen was a novel approach (and) these results are very encouraging, especially in this cohort of women where 75% were platinum-resistant. Equally encouraging was the tolerability, with manageable side effects."

"These data are promising, especially for patients with platinum-resistant disease where effective treatment options are limited," he said. "This was a small trial and its findings would need to be confirmed in a larger randomized trial. This regimen should be utilized by oncologists who are experienced with the use of these agents, especially immunotherapy, which has unique side effects."

The study was supported by Merck and Co. through the Merck Investigator Studies Program. No relevant conflicts were disclosed.

SOURCE: https://bit.ly/3mxK1Ip JAMA Oncology, online November 19, 2020.

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