Ongoing Clinical Trials in Endometrial Cancer
The most clinically relevant ongoing trial mentioned in the evidence is PORTEC 3, which compares concurrent chemoradiation plus adjuvant chemotherapy versus pelvic radiation alone in high-risk and advanced-stage endometrial carcinoma. 1
High-Risk and Advanced-Stage Disease Trials
PORTEC 3 Study
This intergroup trial by the Dutch Cooperative Gynaecologic Oncology Group and UK NCRI is evaluating combined modality treatment for patients with:
- Stage IB grade 3 with lymphovascular space invasion (LVSI) 1
- Stage IC or IIA grade 3 1
- Stage IIB 1
- Stage III disease 1
- Stage IB, IC, II or III with serous or clear cell histology 1
The trial design compares radiotherapy with concomitant and sequential chemotherapy plus radiotherapy versus pelvic radiation alone. 1 This study was designed to resolve conflicting data from Italian and Japanese trials that failed to show survival differences between chemotherapy and radiotherapy. 1
Advanced/Recurrent Disease Trials
GOG-209
This randomized trial is evaluating combination chemotherapy regimens with or without taxanes for advanced or recurrent disease. 1 The trial builds on prior evidence showing that addition of paclitaxel to combination chemotherapy improved progression-free survival (HR = 0.80; 95% CI 0.71–0.90; P = 0.004), though with increased toxicity. 1
Targeted Therapy and Immunotherapy Trials
Bevacizumab Combination Trials
GOG-86P evaluated the addition of bevacizumab, temsirolimus, or ixabepilone to first-line paclitaxel-carboplatin in 349 patients with advanced or recurrent endometrial cancer. 1 Bevacizumab showed superior median overall survival compared to historical controls (34.0 versus 22.7 months, P < 0.039). 1
MITO END-2 trial added bevacizumab to 6-8 cycles of paclitaxel-carboplatin followed by bevacizumab maintenance in 108 patients. 1 This resulted in significant improvement in median progression-free survival (13 versus 8.7 months, P = 0.036) and numerical increase in median overall survival (23.5 versus 18 months, P = 0.24). 1
Biomarker-Driven Trials
Trials targeting PI3K/PTEN/AKT/mTOR pathway, RAS-MAPK, angiogenesis (especially FGFR2 and VEGF/VEGFR), ER/PgR, and homologous recombination deficiency/MSI are warranted. 1 These molecular alterations are present in endometrial cancer and represent promising therapeutic targets. 1
Novel Trial Designs
GOG0261 is evaluating paclitaxel plus carboplatin versus paclitaxel plus ifosfamide in patients with different types of gynecological carcinosarcomas (NCT00954174). 1 A randomized phase II trial of nintedanib versus chemotherapy in patients with recurrent clear-cell carcinoma of the ovary or endometrium (EudraCT 2013-002109-73) is also ongoing. 1
Key Trial Design Considerations
Novel trial designs using alternative early endpoints are being employed, such as the percentage of patients free from progression at 18 weeks, since tumor response to biological agents may not occur to the same degree as with chemotherapy. 1 Better patient selection using systematic biomarker integration and earlier characterization with standardized diagnostic imaging and biomarker assessments are essential. 1
Trials should be biomarker-driven with biopsy at entry, as progress in targeted therapy development is likely to be faster with this approach. 1 The presence of a specific biomarker target may not always reflect probability of response, as demonstrated by phase II studies of mTOR inhibitors showing no correlation between response and PI3K/AKT pathway mutations. 1