The long-running randomized NRG Oncology GOG-258 clinical trial failed to identify an overall survival benefit with adjuvant chemoradiotherapy vs chemotherapy alone in any subgroup of patients with locally advanced endometrial cancer. After a median follow-up of 112 months, the hazard ratio for overall survival with chemoradiotherapy was 1.05. Recurrence-free survival was also not improved with the combination over chemotherapy alone, according to Daniela Matei, MD, of Northwestern University in Chicago, who presented the findings at the 2023 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.1 The addition of radiation therapy did, however, reduce the incidence of locoregional recurrence (vaginal, pelvic, and para-aortic), but distant recurrences were more common with chemoradiotherapy, according to the long-term results.
“For those people who are still skeptical of the role of chemotherapy alone in the treatment of patients with stage III endometrial cancer…, this should put an end to the question.”— Daniela Matei, MD
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The results are the conclusion of an 813-patient study that was almost 2 decades in the making. Dr. Matei noted she was pregnant with her daughter when she proposed NRG Oncology GOG-258, and now her daughter is headed to college. The study opened in 2009 and closed to accrual in 2014.
Dr. Matei said the overall survival data from the study had been “eagerly awaited,” and now with this analysis, the debate should be considered over. “For those people who are still skeptical of the role of chemotherapy alone in the treatment of patients with stage III endometrial cancer…, this should put an end to the question. This is the definitive study to address that question,” she said.
Molecular analysis of potential biomarkers of efficacy is ongoing. “Considering there is no difference in the entire group, it’s hard to imagine we are going to find a subgroup who benefits, but that remains to be seen,” commented Dr. Matei.
NRG Oncology GOG-258
The primary objective of the randomized trial was to determine whether combined systemic cisplatin-based chemotherapy and tumor volume–directed radiation therapy would improve recurrence-free and overall survival vs carboplatin/paclitaxel chemotherapy in surgical stage III/IVA endometrial cancer. Several previous clinical trials explored this question, without settling on an answer.
Among the 813 patients, approximately 75% in each arm had stage IIIC1 or IIIC2 disease. The patients were randomly assigned to receive chemoradiotherapy or chemotherapy alone. The experimental arm consisted of cisplatin at 50 mg/m2 on days 1 and 29 plus volume-directed radiation at 45 Gy with or without brachytherapy, followed by carboplatin area under the curve (AUC) 5 plus paclitaxel at 175 mg/m2 every 21 days for four cycles. The chemotherapy-alone arm involved carboplatin at AUC 6 plus paclitaxel at 175 mg/m2 every 21 days for six cycles.
The previously reported primary analysis occurred at a median follow-up of 47 months.2 At 60 months, the percentage of patients alive and free of relapse was essentially the same: 59% with chemoradiotherapy and 58% with chemotherapy-alone (hazard ratio [HR] = 0.90; 90% confidence interval [CI] = 0.74–1.10; P = .20). Chemoradiotherapy was associated with a lower 5-year incidence of vaginal recurrence (2% vs 7%; HR = 0.36) and pelvic and para-aortic lymph node recurrence (11% vs 20%; HR = 0.43;) than chemotherapy alone, but distant recurrences were more common in women treated with chemoradiotherapy (27% vs 21%; HR = 1.36).
The latest analysis, at a median follow-up of 112 months, documented 134 deaths in the chemoradiotherapy group and 125 in the chemotherapy-alone group (HR = 1.05; 95% CI = 0.82–1.34). Chemoradiotherapy did not improve overall survival compared with chemotherapy in any subgroup, including by stage, histology, body mass index, presence of residual disease, and age. In fact, results for the variables more often tended to favor chemotherapy.
DISCLOSURE: Dr. Matei has served as a consultant to GlaxoSmithKline, CVS Health, AstraZeneca, and Merck; has served as an editor for Elsevier; and has received grant support from PinotBio and Merck.
1. Matei DE, Enserro D, Kudrimoti M, et al: Overall survival in NRG258, a randomized phase III trial of chemo-radiation vs. chemotherapy alone for locally advanced endometrial carcinoma. 2023 SGO Annual Meeting on Women’s Cancer. Presented March 25, 2023.
2. Matei D, Filiaci V, Randall ME, et al: Adjuvant chemotherapy plus radiation for locally advanced endometrial cancer. N Engl J Med 380:2317-2326, 2019.
Kathleen Moore, MD, MS
Kathleen Moore, MD, MS, the Virginia Kerley Cade Endowed Chair in Cancer Developmental Therapeutics and Professor of Gynecologic Oncology at the University of Oklahoma Health Sciences Center, spoke with The ASCO Post about GOG-258. According to Dr. Moore, the final...