Pembrolizumab monotherapy induced durable clinical outcomes in heavily pretreated patients with clear cell gynecologic cancer.
Pembrolizumab (Keytruda) monotherapy induced durable clinical outcomes in heavily pretreated patients with clear cell gynecologic cancer (CCGC), according to findings from the phase 2 PEACOCC trial (NCT03425565).
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.