Patients with heavily pretreated clear cell gynecologic cancer achieved encouraging responses with single-agent pembrolizumab.
Durable clinical outcomes were observed in heavily pretreated patients with clear cell gynecologic cancer (CCGC) following treatment with pembrolizumab monotherapy in the phase 2 PEACOCC trial (NCT03425565), according to findings published in the Annals of Oncology.1
Forty-eight patients were included in the analysis. The progression-free survival (PFS) rate was 43.8% (n = 21/48; 90% CI, 31.5%-56.6%) at 12 weeks, exceeding the established lower bound of 15%. Eighteen (37.5%) patients had progressive disease, and 6 (12.5%) progressed and died.
Translational sample analysis is ongoing. Investigators said these results justify further evaluation of pembrolizumab as the new standard of care for advanced CCGC.
At a median follow-up of 2.1 years, the median PFS was 12.2 weeks (95% CI, 5.9-23.9). The 1-year PFS rate was 22.0% (95% CI, 11.5%-34.7%).
The median overall survival (OS) was 71.0 weeks (95% CI, 29.1-137.6). The OS rate was 54.8% (95% CI, 39.3%-67.8%) at 1 year and 37.2% (95% CI, 22.4%-52.0%) at 2 years.
Prognosis is poor for patients with advanced CCGC. The objective response rate (ORR) for standard second-line chemotherapy ranges from 0% to 8% in ovarian pure clear cell cancer.
Previous data have shown that PD-L1 and PD-L2 are highly expressed in CCGC. Furthermore, PD-L1–positive tumor infiltrating lymphocytes, proinflammatory cytokine signaling, high tumor mutational burden are associated with CCGC and investigators have observed preclinical activity with PD-1 inhibitors in CCGC. Investigators in PEACOCC sought to assess the safety and efficacy of the PD-1 inhibitor pembrolizumab in this patient population.
Eligible patients were diagnosed with advanced clear cell ovarian cancer, including primary peritoneal and fallopian tube disease; endometrial, vaginal, vulval or cervical cancer. They needed to have measurable disease based on RECIST v1.1 criteria as well as evidence of radiological disease progression. Patients had an ECOG performance status of 0 or 1 and received at least 1 prior line of chemotherapy.
Those who received prior therapy with an anti–PD-1, anti–PD-L1, or anti–PD-L2 agent were excluded.
Patients in the trial received 200 mg of pembrolizumab every 21 days for a maximum of 2 years or until progression, unacceptable toxicity, or clinical/patient decision. Four patients remain on treatment.
The median patient age was 58.5 years (range, 32-77). Twenty-six patients had an ECOG score of 0 and 22 had a score of 1. Most patients had ovarian clear cell cancer (85.4%), while 12.5% had endometrial clear cell disease and 2.1% had cervical clear cell disease.
The median range of prior treatments was 2 (range, 1-6). Nineteen (39.6%) received previous antiangiogenic therapy, 43 (89.6%) received previous surgery, and 11 (22.9%) received previous radiotherapy.
The primary end point was PFS at 12 weeks. Key secondary end points were ORR, OS, duration of response (DOR), and safety.
The ORR was 25.0% (90% CI, 15.1%-37.3%) at the February 18, 2022, data cutoff. One patient had a complete response and 11 had a partial response. The median time to response was 9.5 weeks (range, 5.7-23.7).
The median DOR was 48.1 weeks (95% CI, not evaluable). The 1-year DOR rate was 47.7% (95% CI, 14.1%-75.6%).
Investigators observed no grade 4/5 treatment-related adverse effects (TRAEs). Eight (16.7%) patients experienced grade 3 TRAEs and 25 (52.1%) experienced grade 1/2 TRAEs. Three (6.3%) patients discontinued due to TRAEs.
There were 2 cases of grade 3 TRAE hyperthyroidism. Investigators observed a single incidence each of grade 3 increased alanine aminotransferase, increased alkaline phosphatase, anemia, noninfective encephalitis, diabetic ketoacidosis, and stage II acute kidney injury.