Adjuvant Chemoradiotherapy vs Radiotherapy in High-Risk Endometrial Cancer

Key Points

  • Chemoradiotherapy did not significantly improve 5-year overall survival but did improve 5-year failure-free survival.
  • Chemoradiotherapy was associated with significantly more severe adverse events. 

As reported in The Lancet Oncology by de Boer et al, the phase III PORTEC-3 trial has shown no significant improvement in 5-year overall survival with adjuvant chemoradiotherapy vs radiotherapy alone in women with high-risk endometrial cancer. Adjuvant chemoradiotherapy, however, was associated with significantly improved failure-free survival.

Study Details

In the open-label international trial, 660 eligible patients with high-risk disease from 103 sites in the United Kingdom, Australia, New Zealand, Italy, Canada, and France collaborating in the Gynaecological Cancer Intergroup were randomized between November 2006 and December 2013 to receive chemoradiotherapy (n = 330) or pelvic radiotherapy alone (n = 330). Radiotherapy consisted of 48.6 Gy in 1.8 Gy fractions given on 5 days per week. Chemotherapy consisted of 2 cycles of cisplatin 50 mg/m² given during radiotherapy followed by 4 cycles of carboplatin AUC = 5 and paclitaxel 175 mg/m².

Randomization was stratified for study center, lymphadenectomy, stage of cancer, and histologic type. The coprimary endpoints were overall survival and failure-free survival.

Overall and Failure-Free Survival

Median follow-up was 60.2 months. Five-year overall survival was 81.8% in the chemoradiotherapy group vs 76.7% in the radiotherapy group (adjusted hazard ratio [HR] = 0.76, P = .11). Five-year failure-free survival was 75.5% vs 68.6% (HR = 0.71, P = .022).

Adverse Events

Grade ≥ 3 adverse events during treatment occurred in 60% of the chemoradiotherapy group vs 12% of the radiotherapy group (P < .0001). Persistent grade ≥ 2 neuropathy was more common after chemoradiotherapy, with 3-year rates of 8% vs 1% (P < .0001). One death in the radiotherapy group was due to either disease progression or late treatment complications; two deaths in the chemoradiotherapy group and one in the radiotherapy group were due to either intercurrent disease or late treatment-related toxicity.

The investigators concluded, “Adjuvant chemotherapy given during and after radiotherapy for high-risk endometrial cancer did not improve 5-year overall survival, although it did increase failure-free survival. Women with high-risk endometrial cancer should be individually counselled about this combined treatment. Continued follow-up is needed to evaluate long-term survival.”

The study was funded by the Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council, Cancer Australia, L’Agenzia Italiana del Farmaco, and Canadian Cancer Society Research Institute.

Stephanie M. de Boer, MD, of the Department of Radiation Oncology, Leiden University Medical Center, is the corresponding author of The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.