Adjuvant chemotherapy administered during and after radiotherapy is feasible for the treatment of patients with high-risk endometrial cancer despite an increased risk of toxicities compared with radiotherapy alone, a study published in the journal The Lancet Oncology has shown.1
Because approximately 15% of patients with endometrial cancer possess high-risk features and are at an increased risk of distant metastases and cancer-related death, researchers sought to evaluate the efficacy and safety of adjuvant chemoradiotherapy compared with that of radiotherapy alone in women with high-risk endometrial cancer.
For the international, open-label, phase 3 PORTEC-3 trial, investigators enrolled 660 women and randomly assigned them to radiotherapy alone at a dose of 48.6 Gy in 1.8-Gy fractions given 5 times per week or chemoradiotherapy. Chemoradiotherapy consisted of 2 cycles of concurrent cisplatin 50 mg/m2 and 4 adjuvant cycles of carboplatin AUC 5 and paclitaxel 175 mg/m2.
With respect to health-related quality of life, results showed that at a median follow-up of 42.3 months, EORTC QLQ-C30 functioning scales were significantly lower and health-related quality of life symptom scores were higher for patients in the chemoradiotherapy group compared with those in the radiotherapy alone group, meaning those receiving chemoradiotherapy had worse functioning and worse symptoms; however, researchers found that both functioning and symptoms improved with time.
The study demonstrated at 12 and 24 months, global health or quality of life was similar between the 2 treatment arms, while physical function remained slightly worse in patients receiving chemoradiotherapy.
In terms of safety, 25% of patients in the chemoradiotherapy group reported severe tingling or numbness vs 6% of those in the radiotherapy group at 24 months (P <.0001); furthermore, 94% and 44%, respectively, experienced grade 2 or worse adverse events and 61% vs 13%, respectively, reported grade 3 or worse adverse events (P <.0001). Most grade 3 adverse events were hematologic.
At 12 and 24 months, no significant differences in grade 3 or worse adverse events were observed between arms, but grade 2 or worse sensory neuropathy was more common at 24 months in the chemoradiotherapy group (P <.0001).
Although the findings suggest increased risk of toxicities with chemoradiotherapy vs radiotherapy alone, the study demonstrated that adjuvant chemoradiotherapy is feasible in this setting. Analyses of overall survival and failure-free survival will be conducted before final conclusions are made.
1. de Boer SM, Powell ME, Mileshkin L, et al. Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2016 Jul 7. doi: 10.1016/S1470-2045(16)30120-6. [Epub ahead of print]