The phase 2 PEACOCC trial has revealed promising results for pembrolizumab (Keytruda) in treating advanced clear cell gynecologic cancer (CCGC), marking a potential breakthrough for patients with limited treatment options. The study, published in JAMA Oncology, demonstrated significant clinical benefit in previously treated patients.
Key Efficacy Findings
The trial met its primary endpoint with 42% of eligible patients (n=48) achieving disease control and remaining progression-free at 12 weeks (95% CI, 28%-57%). The objective response rate at 12 weeks reached 21% (95% CI, 10%-35%), with the best overall response rate of 25% (95% CI, 14%-40%) including 12 partial responses.
Long-term follow-up data at a median of 46.9 months showed a median progression-free survival of 2.7 months (95% CI, 1.3-5.4) and median overall survival of 14.8 months (95% CI, 6.7-28.2). The one-year overall survival rate was 54%, with 38% of patients surviving at two years.
Patient Population and Treatment Protocol
The study enrolled patients aged 18 and older with various types of CCGC, including ovarian (85%), endometrial (13%), and cervical (2%) cancers. All participants had received at least one prior course of platinum chemotherapy. The median age was 58.5 years, with patients receiving pembrolizumab 200mg intravenously every three weeks for up to 35 cycles.
"The PEACOCC trial showed clinical benefit with pembrolizumab in patients with previously treated advanced CCGC, of whom all except 1 had mismatch repair–proficient [MMR] disease," stated Dr. Rebecca Kristeleit from Guy's and St Thomas' NHS Foundation Trust and colleagues.
Safety and Tolerability Profile
Treatment-related adverse effects were generally manageable, with diarrhea, fatigue, and pruritus being the most common. The median treatment duration was 4.5 cycles, with 81% of discontinuations due to disease progression rather than toxicity.
Notable adverse events included:
- Diarrhea (19% all grades)
- Fatigue (30% all grades)
- Pruritus (21% all grades)
- Hypothyroidism (21% all grades)
Clinical Implications
The results are particularly significant given the poor prognosis typically associated with CCGC and the limited treatment options available. The study's outcomes suggest superior performance compared to historical standard-of-care chemotherapy data, despite the limitation of its single-arm design and moderate sample size.
Dr. Kristeleit's team emphasized that these findings justify further evaluation of pembrolizumab, either as monotherapy or in combination strategies, through randomized clinical trials. Ongoing translational research aims to identify patients most likely to benefit from this treatment approach.
The durability of responses, with a median duration of 13.1 months among responders, particularly stands out as a clinically meaningful outcome for this challenging patient population. These results open new possibilities for immunotherapy in gynecologic cancers, especially in the context of MMR-proficient disease.
