TAMPA – Vaginal cuff brachytherapy followed by paclitaxel and carboplatin chemotherapy was not superior to pelvic radiation therapy in randomized phase III Gynecologic Oncology Group trial 249 involving women with high-intermediate-risk, early stage endometrial cancer.

The 24-month recurrence-free survival was 82% and 84% in 301 women assigned to receive pelvic radiation therapy (PXRT) and 300 women assigned to receive vaginal cuff brachytherapy followed by paclitaxel and carboplatin chemotherapy (VCB/C) for a hazard ratio of 0.97. Survival at 24 months was 93% in the PXRT group and 92% in the VCB/C group (hazard ratio, 1.28), Dr. D. Scott McMeekin reported during a late-breaking abstract session at the annual meeting of the Society of Gynecologic Oncology.

"There was no statistically significant evidence of heterogeneity of treatment effects with respect to recurrence-free survival among stage, age, race, performance status, histology, or lymphadenectomy use in either of the groups," said Dr. McMeekin of the University of Oklahoma, Oklahoma City.

Study subjects were women with a median age of 63 years. All of the women underwent hysterectomy and had either stage I endometrioid disease with high risk based on GOG (Gynecologic Oncology Group) trial 99 study criteria, stage II disease, or stage I-II serous or clear cell tumors. Most (74%) had stage I disease, and 89% underwent lymphadenectomy. Histology was endometrioid type in 71% of patients, serous in 15%, and clear cell in 5%.

All patients participated in quality of life assessments at five time points, and tissue samples were collected for a translational research correlative, he said.

Treatment began within 12 weeks following surgery. Those in the PXRT group were treated using standard four-field or intensity-modulated radiation therapy techniques (with optional VCB for those with serous or clear cell tumors or with stage II disease), and patients in the VCB/C group received high-dose rate or low-dose rate brachytherapy followed by paclitaxel (175 mg/m² over 3 hours) and carboplatin (AUC 6) every 21 days for a total of three cycles.

Treatment was generally well tolerated, with 91% of PXRT patients and 87% of VCB/C patients completing therapy.

"That being said, acute adverse effects were more frequent and tended to be more severe in patients receiving VCB/C," Dr. McMeekin said, noting that the extent to which that affected quality of life is the subject of an analysis currently underway; those data are forthcoming.

Early-stage endometrial cancer poses a variety of clinical challenges, Dr. McMeekin said.

"Who is at risk? How is that risk defined? Which modalities reduce risk in which populations?" he said, noting that the information used on a day-to-day basis to help in decision making includes patient age and history, tumor grade, uterine characteristics, and nodal status.

Prior studies, including GOG 99 (Gyn. Oncol. 2004;92:744-51), have helped create risk models to identify patients at greater recurrence risk who might benefit most from adjuvant therapy such as pelvic radiation therapy. Risk criteria in GOG 99 were based on age and the number of risk factors, and while that study showed that pelvic radiation therapy reduced risk (and concluded that adjunctive radiation therapy in early-stage, intermediate-risk disease decreased the risk of recurrence, but should be limited to patients with high-intermediate risk), it also helped define patterns of failure, suggesting that distant sites of failure were "greater than we perhaps recognized," Dr. McMeekin said.

That, in turn, introduced the idea that a systemic therapy might improve outcomes, he added.

Chemotherapy moved to the forefront based on findings from GOG 122, which showed significant improvement in progression-free survival and overall survival with chemotherapy vs. whole abdomen radiation therapy in stage III and IV endometrial cancer, he said.

A number of uncontrolled studies have also suggested that chemotherapy may benefit other populations at increased risk, including patients with serous and clear cell stage I disease, who have a broad risk of recurrence ranging from 15% to 50% depending on disease and patient characteristics, and stage II patients, who have increased risk of loco-regional failure and progression-free survival rates comparable to those seen in high- intermediate-risk populations, he said.

The current study was initiated in light of these findings, but the investigators "could not identify subgroups for whom one therapy appeared to be more or less effective," Dr. McMeekin said.

He noted that the use of radiation therapy plus chemotherapy has been evaluated, including in two studies that demonstrated improved progression-free but not overall survival in patients with stage I-III disease.

"This is also the subject of the ongoing PORTEC-3 study, he said.

The current findings, which showed that "even in an enriched population, most patients did well," suggest that refinement is needed with respect to factors that define risk, he said, noting that selection based on clinical pathologic features and molecular profiling are underway both in the current study and another GOG study (GOG 210).

Dr. McMeekin reported having no disclosures.

Vaginal cuff brachytherapy plus chemotherapy no better than pelvic radiation in early endometrial cancer