Pembrolizumab/Bevacizumab Achieves Nearly 48% ORR in Recurrent Ovarian Cancer

A combination of pembrolizumab (Keytruda) and bevacizumab (Avastin) offers another treatment approach for patients with heavily pretreated recurrent epithelial ovarian cancer (EOC), particularly those with the clear cell subtype, according to a new retrospective study published in the European Journal of Gynaecological Oncology.¹ The regimen appears to maintain encouraging efficacy while sidestepping the significant toxicities associated with 3-drug combinations that include chemotherapy.

Investigators reported an objective response rate (ORR) of 41.7% in 12 evaluable patients, with 1 patient achieving a complete response with normalization of tumor markers. In particular, patients with ovarian clear cell carcinoma (OCCC), a subtype known for its poor prognosis and resistance to conventional chemotherapy, achieved an ORR of 66.7%.

“This study differs from prior trials by evaluating pembrolizumab and bevacizumab as a 2-drug regimen, potentially offering a less toxic alternative,” wrote Wang S-Y, et al. “The favorable tolerability profile… may be attributed to the use of bevacizumab, which has a low toxicity profile, and the absence of cyclophosphamide.”

What Were the Patient Demographics?

The retrospective study evaluated patients with recurrent EOC from January 2018 to December 2021. Patients were a mean age of 55.8 years (range, 39-69), 75% were diagnosed with advanced-stage (FIGO III–IV) disease, and the majority (58%) had an ECOG performance status of 1. The mean number of previous chemotherapy regimens was 3.8, with 7 patients (58.3%) having received more than 3 lines of chemotherapy.

PD-L1 status was positive in a quarter of patients, negative in half, and unknown in the remainder. The vast majority were platinum-sensitive at the time of recurrence.

Patients received intravenous pembrolizumab plus bevacizumab every 3 weeks. The primary outcome was ORR, assessed primarily using the Gynecological Cancer Intergroup (GCIG) criteria based on serum CA-125 levels. For patients with normal baseline CA-125, response was evaluated using immune-related RECIST (irRECIST) criteria on CT or MRI scans. Secondary outcomes included progression-free survival (PFS) and overall survival (OS).

Notably, none of the 6 patients with high-grade serous carcinoma responded; 3 patients showed no response, and 3 had disease progression. The median PFS for the study population was 2.8 months (95% CI, 0.7–12.2).

While the small sample size limits definitive conclusions, survival trends favored OCCC. The median PFS for patients with OCCC was 11.6 months (95% CI, −22.2 to 52.4) versus 2.6 months (95% CI, 0.4–6.7) for non-OCCC patients (P =.05).

A trend towards improved OS was also observed in OCCC patients with a median OS that was non-reachable (95% CI, −2.6 to 47.9) compared with a median OS of 6.6 months (95% CI, 4.1–19.5) in non-OCCC patients (P =.07).

What Was the Safety Profile?

No grade 4 adverse events were reported, and notably, no patients required treatment interruption or discontinuation due to toxicity. Grade 1/2 events occurred in 41.7% of patients, with the most common being dyspnea, followed by nausea, diarrhea, rash, and pruritus (all 16.7%). Grade 3 events occurred in a third of patients, with lymphopenia (25.0%) being the most frequent. This tolerability stands in stark contrast to previous studies incorporating oral cyclophosphamide, which reported much higher rates of severe adverse events leading to dose interruptions in over 40% of patients.

The investigators noted a number of limitations of the study including its retrospective design, small sample size, and lack of control cohort. They urged the need for larger, prospective trials to validate these findings. Further, they acknowledge that future studies must focus on recruiting larger cohorts, particularly of patients with OCCC, and incorporate comprehensive genomic profiling to identify predictive biomarkers.

REFERENCE:

1. Wang S-Y, Chou Y-T, Wen K-C, et al. Combined pembrolizumab and bevacizumab therapy in heavily treated recurrent ovarian cancer. Eur J Gyn Oncol. 2025;46;8:48-57. doi:10.22514/ejgo.2025.108