Does Adjuvant Chemoradiotherapy Extend Relapse-Free Survival in Stage III or IVA Endometrial Cancer?
In the phase III GOG 258 trial reported in The New England Journal of Medicine, Matei et al found that 6 months of adjuvant platinum-based chemotherapy plus radiation therapy did not improve relapse-free survival vs chemotherapy alone in stage III or IVA endometrial cancer.
In the open-label trial, 736 eligible patients were randomly assigned between June 2009 and July 2014 to receive adjuvant chemoradiotherapy or chemotherapy alone. Chemoradiotherapy consisted of cisplatin at 50 mg/m2 on days 1 and 29 with volume-directed external-beam radiation therapy followed by carboplatin at AUC 5 to 6 plus paclitaxel at 175 mg/m2 every 21 days for four cycles with granulocyte colony-stimulating factor support.
Radiotherapy was delivered to the pelvis with or without para-aortic fields with a planned total dose of 4,500 cGy in 25 fractions at 180 cGy per fraction. The chemotherapy group received carboplatin at AUC 6 plus paclitaxel at 175 mg/m2 every 21 days for six cycles.
Relapse-Free Survival
The primary endpoint was relapse-free survival. The total of 736 eligible patients were included in the analysis of relapse-free survival; of these patients, 707 received the randomly assigned intervention (346 received chemoradiotherapy, and 361 received chemotherapy). Median follow-up was 47 months.
At 60 months, estimated relapse-free survival was 59% in the chemoradiotherapy group and 58% in the chemotherapy group (hazard ratio [HR] = 0.90, P = .20). The chemoradiotherapy group had a lower 5-year incidence of vaginal recurrence (2% vs 7%, HR = 0.36, 95% confidence interval [CI] = 0.16–0.82) and pelvic and para-aortic lymph node recurrence (11% vs 20%, HR = 0.43, 95% CI = 0.28–0.66), but an increased risk of distant recurrence (27% vs 21%, HR = 1.36, 95% CI = 1.00–1.86).
Adverse Events
Grade ≥ 3 adverse events occurred in 58% of patients in the chemoradiotherapy group and 63% in the chemotherapy group. Constitutional symptoms, fatigue, gastrointestinal events, renal or genitourinary events, and musculoskeletal events were significantly more common per grade in the chemoradiotherapy group, whereas hematologic adverse events were significantly more common and more severe in the chemotherapy group. Two deaths in the chemotherapy group were considered related to treatment (due to sepsis and sudden death).
The investigators concluded, “Chemotherapy plus radiation was not associated with longer relapse-free survival than chemotherapy alone in patients with stage III or IVA endometrial carcinoma.”
Disclosure: The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit nejm.org.
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