A combined modality regimen did not increase recurrence-free survival (RFS) in patients with optimally debulked stage III/IVA endometrial carcinoma. The open-label randomized phase III trial compared treatment with cisplatin and tumor volume-directed radiation followed by carboplatin and paclitaxel for four cycles (C-RT) versus carboplatin and paclitaxel treatment for six cycles (CT). Even though C-RT reduced the rate of local recurrence compared to CT, C-RT did not increase RFS, Daniela Matei, MD, of Northwestern University, said at the Gynecologic Cancer Oral Abstract Session on June 2 (Abstract 5505).
The GOG 258 trial enrolled and randomly assigned 813 patients to one of the two treatment arms between June 2009 and July 2014, with 407 patients assigned to the C-RT arm and 406 assigned to the CT arm. Patient characteristics were well balanced between the two arms of the trial, and median follow-up was 47 months. The primary endpoints were RFS and death, with a 28.5% reduction in rate of recurrence or death considered significant. Secondary objectives were overall survival (OS), acute and late toxicities, and quality of life, Dr. Matei said.
Seventy-five percent of the patients in the C-RT arm completed the study therapy versus 85% in the CT arm. Acute toxicities were similar for the two arms of the trial. Grade 3 or higher adverse events included gastrointestinal (13% with C-RT vs. 4% with CT; p < 0.01); metabolic (15% vs. 9%); neurologic (7% vs. 5%); blood/bone marrow (40% vs. 52%); and infectious (4% vs. 5%). There were no grade 5 adverse events in the C-RT arm versus three in the CT arm.
Dr. Matei reported that treatment with C-RT reduced the vaginal recurrence incidence at 5 years by 3% versus 7% in the CT arm (HR 0.36, 95% CI [0.16, 0.82]). Pelvic and para-aortic recurrences were also reduced in the C-RT arm (10%) compared with the CT arm (19%; HR 0.43, 95% CI [0.28, 0.66]). Distant recurrences, however, were more common with C-RT (27%) versus CT (21%; HR 1.36, 95% CI [1.00, 1.86]).
Trial results found that the combined modality regimen did not improve RFS compared to chemotherapy (HR 0.9, 95% CI [0.74,1.1]).
The estimates for 5-year OS are 70% for the C-RT arm versus 73% for the CT arm. The data cutoff was March 9, 2017, making these data not yet mature for final analysis. Dr. Matei said the survival and quality-of-life endpoints will be reported in the future.
Discussant Timothy N. Showalter, MD, MPH, of the University of Virginia School of Medicine, said that he would like to encourage investigators to consider leaving in chemoradiation therapy when they pursue novel strategies and optimized outcomes given the results from GOG 258.
“It is important to remember that GOG 258 and prior studies have also demonstrated a strong effect of radiation therapy on preventing regional nodal and local recurrences,” he said. “There are still radiation questions on the table; for example, in GOG 258 we have seen the cumulative incidence of both para-aortic and pelvic recurrences.”
Potential designs of clinical trials will include radiation therapy, Dr. Showalter said. “On the heels of excellent data provided by GOG 258, rather than simply leaving radiation therapy out and focusing on chemotherapy-alone options, one should consider designs such as this where the options include both systemic therapy without a radiation-first arm in the trial design but still leaving in radiation therapy.”
These trials have demonstrated the strong effect of radiation therapy on local-regional recurrence (LRR). “Future clinical trials should not step backward for LRR,” he said.