Adjuvant Chemotherapy plus Radiation for the Treatment of Locally Advanced Endometrial Cancer - PDF Version

Matei D., Filiaci V., Randall M.E., Mutch D., Steinhoff M.M., Di Silvestro P.A., Moxley K.M., Kim Y.M., Powell M.A., O'Malley D.M., Spirtos N.M., Small W. Jr, Tewari K.S., Richards W.E., Nakayama J., Matulonis U.A., Huang H.Q., Miller D.S.

N Engl J Med., 2019, Jun 13;380(24):2317-2326. doi: 10.1056/NEJMoa1813181.

BACKGROUND:

Stage III or stage IVA endometrial cancer carries a significant risk of systemic and locoregional recurrence.

METHOD:

In this randomised phase 3 trial, we tested whether treatment that involved six months of platinum-based chemotherapy plus radiation therapy (chemoradiotherapy) was associated with a longer relapse-free survival period (primary end-point) than treatment through six cycles of combination chemotherapy alone in patients with stage III or stage IVA endometrial carcinoma. Secondary end-points included overall survival, acute and chronic toxic effects, and quality of life.

RESULTS:

Of the 813 patients enrolled in the trial, 736 were eligible for study and were included in the analysis of relapse-free survival. Of those patients, 707 received the randomly assigned intervention. Among these, 346 received chemoradiotherapy and 361 received chemotherapy only. The median follow-up period was 47 months. At 60 months, the Kaplan-Meier estimate of the percentage of patients who were alive and relapse-free was 59% (95% confidence interval [CI], 53 to 65) for the chemoradiotherapy group, and 58% (95% CI, 53 to 64) for the chemotherapy-only group (hazard ratio, 0.90; 90% CI, 0.74 to 1.10). Chemoradiotherapy was associated with reduced recurrence of vaginal carcinoma after five years compared with chemotherapy alone  (2% vs. 7%; hazard ratio, 0.36; 95% CI, 0.16 to 0.82) and reduced recurrence of pelvic and para-aortic lymph-node cancer (11% vs. 20%; hazard ratio, 0.43; 95% CI, 0.28 to 0.66). However, distant recurrence was more common in association with chemoradiotherapy (27% vs. 21%; hazard ratio, 1.36; 95% CI, 1.00 to 1.86). Adverse events of grades 3, 4, or 5 were reported in 202 patients (58%) who were in the chemoradiotherapy group and 227 patients (63%) in the chemotherapy-only group.

CONCLUSION:

In patients with stage III or stage IVA endometrial carcinoma, chemotherapy plus radiation was not associated with longer relapse-free survival periods than chemotherapy alone.