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Chemoradiotherapy (CRT) appeared to be no better than chemotherapy alone as adjuvant treatment for women with locally advanced endometrial cancer, the phase III GOG 258 trial found.

At 5 years, 59% of women in the CRT arm were estimated to be alive and relapse-free compared with 58% in the chemotherapy-alone arm (HR 0.90, 90% CI 0.74-1.10, one-sided P=0.20), reported Daniela Matei, MD, of Northwestern University Feinberg School of Medicine in Chicago, and colleagues in the .

"The results of this study support that chemotherapy alone should remain the standard of care for stage III uterine cancer," Matei said in an at Northwestern.

CRT was associated with fewer vaginal recurrences compared with chemotherapy alone (2% vs 7%, respectively) and less frequent pelvic and paraaortic lymph-node recurrence (11% vs 20%). But these benefits were offset by increases in distant recurrence (27% vs 21%), possibly because fewer patients were able to complete their planned treatment in the CRT arm compared with the chemotherapy-alone arm.

Reached for their thoughts on the findings, radiation oncologists not involved in the research did not hold the same view.

"It is clear from the relapse patterns and lack of benefit of chemotherapy over chemoradiotherapy that both therapies are warranted," said Akila Viswanathan, MD, MPH, of Johns Hopkins Radiation Oncology and Molecular Radiation Sciences in Baltimore.

Ann Klopp, MD, of MD Anderson Cancer Center in Houston, told 妖姬直播 that the addition of radiation importantly helped control pelvic and vaginal recurrence, as these can be morbid and difficult to curatively treat.

"Chemoradiation remains a standard option, especially for women who are at a high risk for pelvic recurrence, such as those with high-grade tumors, deep myometrial invasion, or multiple positive pelvic nodes," she said.

Overall survival data were immature at the time of data cutoff, with 86 deaths in the CRT arm and 79 in the chemotherapy-alone arm (73% and 81%, respectively, due to disease progression).

"This trial will be debated in the short- and long-term," Matei said. "This will be a difficult change because radiation has been used historically in this group of patients and clearly has a role reducing the rates of local pelvic recurrence."

showed chemotherapy to be superior to whole-abdominal radiation alone in patients with advanced endometrial cancer, but locoregional recurrences occurred in up to one-fifth of patients, which led investigators to hypothesize that CRT could cut down on both local and distant disease recurrence.

"The trial was supposed to be a positive trial demonstrating that the combined regimen was superior to chemotherapy given alone," Matei said.

Viswanathan told 妖姬直播 that use of chemoradiotherapy in stage III endometrial cancer increased following the results of the international , which compared CRT with radiation alone in stage I-III endometrial cancer. The study showed improved failure-free survival at 5 years for CRT over radiation alone in the total study population (HR 0.71), which appeared to be driven by the roughly 45% of patients with stage III disease (HR 0.62) .

"This trial combines two very different stages, but it is patients with stage III disease for which the greatest question still remains -- that is, how can patients adequately have both local and distant relapses prevented by giving combination chemoradiotherapy?" she said.

Matei told 妖姬直播 that the PORTEC 3 results in the stage III group help validate "the role of chemotherapy for this patient group," seen in the current study.

From 2009 to 2014, the phase III GOG 258 study enrolled 736 eligible patients with primarily Federation of Gynecology and Obstetrics (FIGO) stage III endometrial cancer (97.6% in CRT arm; 96.5% in chemotherapy arm). A small number with stage IVA disease were also included, as were stage I/II patients with serous or clear-cell endometrial cancers and positive peritoneal washings.

The CRT group (n=346) received cisplatin plus volume-directed radiation therapy (with or without vaginal cuff brachytherapy) followed by carboplatin plus paclitaxel for a total of four cycles. The chemotherapy group (n=361) received carboplatin plus paclitaxel for six cycles.

Statistically, quality-of-life measures as assessed by the Trial Outcome Index were significantly worse in the CRT group compared with the chemotherapy group. But with the least-squares mean score 5.2 points lower at 18 weeks and 3.4 points lower at 70 weeks, neither surpassed the predetermined level for a clinically important difference (6 points).

Neurotoxicity was seen in both arms of the study, and on the FACT/GOG-NTX subscale were significantly worse with chemotherapy alone, with the least-squares mean score 2.0 points lower than the CRT group (1.2 points representing a clinically important difference for this scale).

Klopp noted that the grade 3-5 toxicity was similar between the two groups, with "predictably" more gastrointestinal toxicity in patients receiving pelvic radiation and more neurotoxicity for those treated with the longer course of chemotherapy.

Acute grade ≥3 adverse events (AEs) were similar between the two groups, 63% with chemotherapy alone and 58% with CRT, but acute grade ≥4 AEs were twice as frequent in the chemotherapy-alone group (30% vs 14%). Acute AEs of any grade were more frequent in the CRT arm and included gastrointestinal and musculoskeletal events, constitutional symptoms, fatigue, and kidney or genitourinary events. Hematologic AEs were more frequent with chemotherapy alone.

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