According to the results of the Phase II PEACOCC trial (NCT03425565) reported by the 2022 ESMO Conference, pembrolizumab monotherapy induced lasting clinical outcomes in patients with severely treated clear cell gynecological tumors (CCGC) (Abstract #521MO). Patients with advanced CCGC in
have poor prognosis, and the objective response rate (ORR) of standard second-line chemotherapy is between 0% and 8%. Preclinical studies have shown that PD-1 inhibitors are active in CCGC. PEACOCC is a phase II, multicenter, single-arm, academic clinical trial conducted in the UK. Patients with advanced CCGC who had undergone ≥1 line of chemotherapy (PD), excluding patients who had previously received anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs.
This trial evaluated the safety and effectiveness of the PD-1 inhibitor pembolizumab in the CCGC patient population. Enrolled patients received 200 mg pembolizumab every 21 days for up to 2 years until disease progression, unacceptable toxicity, or clinical/patient decision. Four patients are still receiving treatment. The median age of the patient was 58.5 years (range 32-77 years). The ECOG PS score was 0 in 26 patients and 1 in 22 patients. Most patients had ovarian clear cell carcinoma (85.4%), 12.5% were endometrial clear cell carcinoma, and 2.1% were cervical clear cell carcinoma. The median range of previous treatment lines was 2 (range 1-6). 19 cases (39.6%) had previously received antiangiogenesis treatment, 43 cases (89.6%) had previous surgery, and 11 cases (22.9%) had previous radiotherapy. The primary endpoint was progression-free survival at 12 weeks (PFS). Key secondary endpoints are ORR, overall survival (OS), duration of mitigation (DOR), and security.
baseline characteristics
efficacy
- 8 patients were included in the analysis. The PFS rate at 12 weeks was 43.8% (n=21/48; 90% CI: 31.5%-56.6%), exceeding the pre-set 15% lower limit. 18 (37.5%) patients had disease progression (SD), and 6 (12.5%) patients had disease progression and death.
12 week PFS rate
- 8 median follow-up for 2.1 years, with a median PFS of 12.2 weeks (95% CI: 5.9-23.9). The 1-year PFS rate was 22.0% (95% CI: 11.5%-34.7%).
- median OS was 71.0 weeks (95% CI: 29.1-137.6). The 1-year OS rate was 54.8% (95% CI: 39.3% ~ 67.8%) and the 2-year OS rate was 37.2% (95% CI: 22.4% ~ 52.0%).
PFS and OS
- As of February 18, 2022, the ORR was 25.0% (90% CI: 15.1%-37.3%), of which 1 patient had a complete response (CR) and 11 patients had a partial response (PR). Median to remission time was 9.5 weeks (range 5.7-23.7).
- median DOR was 48.1 weeks (95% CI: not evaluable). The 1-year DOR rate was 47.7% (95% CI: 14.1% ~ 75.6%).
ORR and DOR
Safety
- Researchers did not observe grade 4/5 treatment-related adverse reactions (TRAEs). Eight (16.7%) patients experienced grade 3 TRAEs, and 25 (52.1%) patients experienced grade 1/2 TRAEs. Pembrolizumab was discontinued due to TRAEs in 3 patients (6.3%).
- patients suffered from grade 3 hyperthyroidism. The researchers observed a single case of grade 3 alanine transaminase, alkaline phosphatase , anemia , non-infectious encephalitis, diabetic ketoacidosis and stage II acute renal injury.
Safety
PEACOCC trial showed that pembolizumab is a highly effective therapy for patients with advanced CCGC who have received severe treatment, allowing 43.8% of patients to survive at 12 weeks without progress. Sample-based translational research analysis is underway. The above results demonstrate the need to further evaluate pembrolizumab as a new treatment standard for advanced CCGC.
Reference
. Kristeleit R, Clamp A, Gourley C, et al. Efficacy of pembrolizumab monotherapy for advanced clear cell gynaecological cancer: phase II PEACOCC trial. Ann Oncol. 2022;33(suppl 7):S783. doi:10.1016/j.annonc.2022.07.649
