Chemotherapy Added to RT Prolongs FFS in Stage III Endometrial Cancer

Chemotherapy Added to RT Prolongs FFS in Stage III Endometrial Cancer

Dr. Stephanie M. de Boer presents Abstract 5502.
A combination of chemotherapy and radiotherapy prolonged 5-year failure-free survival (FFS) among patients with high-risk, stage III endometrial cancer compared with radiotherapy alone, but no improvement was observed for high-risk stage I or II tumors, according to results presented during the Gynecologic Cancer Oral Abstract Session held June 2 (Abstract 5502).

Patients with stage III endometrial cancer experienced an 11% FFS benefit with the combination treatment compared with those who received radiotherapy alone, Stephanie M. de Boer, MD, of Leiden University Medical Center, in the Netherlands, reported.

The PORTEC-3 trial was an open-label, multicenter, phase III trial that randomly assigned 686 women with high-risk endometrial cancer (stage I, grade 3 with deep myometrial invasion and/or lymph-vascular space invasion; stage II or III cancers; or stage I to III serous or clear cell cancers) to radiotherapy alone (1.8-Gy fractions 5 per week) or a combination of radiotherapy and chemotherapy (two cycles of cisplatin 50 mg/m2 in weeks 1 and 4 of radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m2 at 3-week intervals).

After 3 years, there was a trend of improved overall survival (OS) among patients receiving combination treatment, Dr. de Boer said, with a 5-year OS of 82% in the combined treatment arm and 77% among those receiving radiotherapy alone (hazard ratio [HR] 0.79, 95% CI [0.57, 1.12]; p = 0.18).

There was a trend for improved FFS after 1 year among patients receiving the combination treatment compared with those receiving radiotherapy alone, which resulted in a 5-year FFS of 76% in the combined arm compared with 69% in the radiotherapy arm (HR 0.77, 95% CI [0.58, 1.03]; p = 0.078).

Patients with stage III disease, compared with earlier stage disease, had lower 5-year rates of FFS (64% vs. 79%, respectively; p < 0.001) and OS (74% vs. 83%, respectively; p = 0.003).

However, she said, patients with stage III cancer experienced the greatest benefit from the combined therapy, with a 5-year FFS of 69% compared with 58% for the radiotherapy group (HR 0.66, 95% CI [0.45, 0.97]; p = 0.032). The 5-year OS rate was 79% in the combination arm compared with 70% in the radiotherapy arm (HR 0.69, 95% CI [0.44, 1.09]; p = 0.114).

As reported in Lancet Oncology last year, women receiving chemotherapy experienced significantly greater toxicity and worse functioning and health-related quality of life during and up to 6 months after treatment compared with those receiving radiotherapy alone.

However, “there was rapid recovery at 1 and 2 years, with no differences in quality of life and small differences in physical functioning,” Dr. de Boer said. The physical functioning difference was likely due to sensory neuropathy, which was reported 2 years after randomization by 25% of patients in the combination arm compared with 6% in the radiotherapy arm.

These results suggest that combination therapy should not be used among women with stage I and II cancers, but is a good option for those with stage III disease given its potential to maximize FFS, Dr. de Boer said.

Discussant Ritu Salani, MD, of The Ohio State University, said the trial raises several questions. Should chemotherapy be provided before radiotherapy? Should patient populations be separated by stage and histology? Should maintenance therapies be considered in this population? And what is the role of targeted therapies, checkpoint inhibitors, and endocrine inhibitors as front-line therapy for these cancers?

“We continue to have many treatment options and our tumor board debates will continue,” Dr. Salani said. “PORTEC-3 will add to this discussion, but at this point we are left with individualizing treatment and continuing to provide the best clinical outcomes for our patients while reducing toxicity.”

–​Debra Gordon, MS