A phase 2 non-randomised clinical trial has demonstrated the potential benefits of pembrolizumab in patients with advanced clear cell gynaecological cancers (CCGCs), a subgroup historically associated with poor prognosis and limited treatment options. The PEACOCC trial, conducted across five UK centres, marks a significant step towards expanding therapeutic options for this challenging cancer subtype.
The PEACOCC trial enrolled 48 patients between March 2019 and October 2021, all of whom had histologically confirmed advanced CCGC and had experienced disease progression following at least one prior chemotherapy regimen. Patients received pembrolizumab at a dose of 200 mg intravenously every 21 days for up to two years, with the possibility of retreatment upon disease progression if a stable or partial response had been achieved.
The study met its primary endpoint, with a 12-week progression-free survival (PFS) rate of 42% (95% CI, 28-57), exceeding the predefined efficacy threshold. The objective response rate was 25%, with 12 patients achieving partial responses. The median duration of response was 13.1 months, and the median overall survival (OS) was 14.8 months (95% CI, 6.7-28.2). Importantly, the treatment was well-tolerated, with 19% of patients experiencing grade 3 adverse events and no grade 4 or 5 toxicities reported.
The trial predominantly included patients with mismatch repair (MMR)-proficient tumours, suggesting pembrolizumab’s efficacy extends beyond MMR-deficient cases, which are typically more responsive to immunotherapy.
These findings support pembrolizumab as a viable treatment option for advanced CCGC, offering durable responses and a favourable safety profile. Given the historically low response rates to second-line chemotherapy (<8%), pembrolizumab could represent a new standard of care pending further validation.
The PEACOCC trial’s promising results warrant further investigation through randomised clinical trials to confirm pembrolizumab’s efficacy in a broader patient population. Additionally, the study highlights the need for biomarker-driven research to identify which patients are most likely to benefit from PD-1 inhibition.
For detailed methodology and statistical analysis, refer to the full study published in JAMA Oncology.
Paper: Kristeleit RDevlin MClamp A, et al. Pembrolizumab in Patients With Advanced Clear Cell Gynecological Cancer: A Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. Published online February 06, 2025. doi:10.1001/jamaoncol.2024.6797. Access online here.
