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Triplet appears safe, effective for gynecologic cancers



– Pembrolizumab plus bevacizumab and oral metronomic cyclophosphamide can be effective in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, a phase 2 trial suggests.

The tumor response rate observed with the three-drug regimen (40%) was better than response rates previously reported for pembrolizumab monotherapy (8%) and bevacizumab plus cyclophosphamide (24%), according to Emese Zsiros, MD, PhD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

The combination proved “very safe” and was associated with “excellent quality of life,” she said at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Dr. Zsiros and her colleagues enrolled 40 patients on a phase 2 trial (NCT02853318) of pembrolizumab, bevacizumab, and oral cyclophosphamide in recurrent, advanced-stage epithelial ovarian, fallopian tube, or primary peritoneal cancer. The trial had a safety lead-in cohort of five patients.

At baseline, the mean patient age was 62.2 years (range, 44.9-88.7 years). Most patients (82.5%, n = 33) had high-grade serous histology. The patients had received a mean of 3.2 (range, 1-12) prior lines of chemotherapy. Most patients (75%, n = 30) were platinum resistant, but 10 patients (25%) were platinum sensitive and declined platinum-based therapy.

Study treatment consisted of IV pembrolizumab at 200 mg plus IV bevacizumab at 15 mg/kg every 3 weeks and oral cyclophosphamide at 50 mg every day. Patients were treated until disease progression or unacceptable toxicity.


“The triple regimen was, overall, really well tolerated,” Dr. Zsiros said.

The most common grade 1/2 treatment-related adverse events (AEs) were fatigue (n = 14), diarrhea (n = 13), nausea (n = 9), hypertension (n =7), white blood cell decrease (n = 6), and arthralgia (n = 6).

Grade 3 related AEs included hypertension (n = 5), lymphocyte count decrease (n = 3), and white blood cell decrease (n = 1). There was one grade 4 drug-related AE of decreased lymphocyte count.

The overall response rate was 40%, with all 16 responders having a partial response. The rate of stable disease was 55% (n = 22).

“Only 2 patients out of the 40 progressed after initiation of the treatment, and I would like to point out that both of these patients had a very large disease burden,” Dr. Zsiros said.

She also noted that more than 77% of patients had a decrease in tumor size from baseline.

The disease control rate (partial response plus stable disease) was 95.0% (n = 38) initially and 62.5% (n = 25) at 6 months. However, three patients had not yet reached 6 months follow-up at the data cutoff.

“I would like to point out that 30% of the patients [n = 12] derived an especially long-term clinical benefit over 12 months and 12 cycles of treatment,” Dr. Zsiros said.

She added that quality of life assessment revealed “high physical, emotional, cognitive, and social functioning throughout the clinical trial.” The researchers also observed significantly improved body image from baseline (P less than .002).

Dr. Zsiros reported relationships with Iovance Biotherapeutics and AstraZeneca. The trial was sponsored by Roswell Park Cancer Institute in collaboration with the National Cancer Institute.

SOURCE: Zsiros E et al. SGO 2019, Abstract LBA4.

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