Pembrolizumab Monotherapy May Provide Clinical Benefit in Advanced Clear Cell Gynecological Cancer

Pembrolizumab (Keytruda) monotherapy improved outcomes and prolonged survival in patients with advanced clear cell gynecological cancer (CCGC) who had progressed after at least 1 prior line of chemotherapy, according to results from the phase 2 PEACOCC trial (NCT03425565).

In this multicenter, single-arm trial, single-agent pembrolizumab resulted in a progression-free survival (PFS) rate of 43.8% (90% CI, 31.5%-56.6%) at 12 weeks, exceeding the pre-stated lower bound of 15%. Responses proved durable and treatment remained tolerable with limited toxicity and no grade 4 or greater treatment-related adverse effects (TRAEs).

“The PEACOCC trial indicates that [pembrolizumab monotherapy] is a highly effective therapy in heavily pre-treated patients with advanced CCGC: 43.8% [of patients] were alive and progression-free at 12 weeks. Furthermore, clinical outcomes were durable with limited toxicity,” investigators wrote. “These promising results justify consideration of pembrolizumab monotherapy as a new standard-of-care for advanced CCGC.”

The trial enrolled 49 patients with advanced CCGC who had measurable disease per RECIST v1.1 over 2.5 years, of whom 48 were evaluable at the time of analysis. To be included, patients must have had PD-1/PD-L1 inhibitor–naïve disease. Fresh tissue and archival biopsies were mandatory. The study population had a median age of 58.5 years (range, 32-77 years) with and median of 2 (range, 1-6) lines of prior treatment. ECOG performance status scores were roughly evenly distributed, with 54.2% of patients at 0 and 45.8% at 1. Most patients (n = 41; 85.4%) had ovarian CCGC, with the remainder having either endometrial (n = 6; 12.5%) or cervical (n = 1; 2.1%) CCGC. A minority of patients (n = 19; 39.6%) had received previous antiangiogenic therapy whereas most (n = 43; 89.6%) had previously undergone surgery.

Patients were assigned to receive intravenous pembrolizumab at 200 mg every 21 days for a maximum of 2 years or until disease progression, unacceptable toxicity, or withdrawal of consent.

In addition to the primary end point of PFS rate at 12 weeks, investigators assessed median PFS and median overall survival (OS) as secondary end points. Data showed a median PFS of 12.2 weeks (95% CI, 5.9-23.9) and a median OS of 71 weeks (95% CI, 29.1-137.6) after a median follow-up of 2.1 years. Moreover, the 1- and 2-year OS rates were found to be 54.8% (95% CI, 39.3%-67.8%) and 37.2% (95% CI, 22.4%-52.0%), respectively. Data also showed an overall response rate (ORR) of 25% (90% CI, 15.1%-37.3%) and a median time to response of 9.5 weeks (range, 5.7-23.7). The treatment resulted in 1 complete response, 11 partial responses, and 10 instances of stable disease.

TRAEs were either grade 1 (25%), grade 2 (27.1%), or grade 3 (16.7%) in severity. Hyperthyroidism occurred in 2 patients (4.2%) and was the only grade 3 TRAE to affect more than 1 patient.

“Clinical outcomes were durable with limited toxicity,” investigators concluded.

A translational analysis of samples gathered in this trial is ongoing. Overall, PEACOCC suggests a possible new standard-of-care for advanced CCGC and may justify larger and more conclusive studies of pembrolizumab monotherapy in the future.

Reference

Kristeleit R, Clamp AR, Gourley C, et al. Efficacy of pembrolizumab monotherapy (PM) for advanced clear cell gynaecological cancer (CCGC): Phase II PEACOCC trial. Ann Oncol. 2022;33(suppl 7):521MO. doi:10.1016/j.annonc.2022.07.649