Treatment with vaginal cuff brachytherapy plus paclitaxel and carboplatin chemotherapy was not found to be superior to pelvic radiation therapy in patients with high-intermediate and high-risk early-stage endometrial cancer, according to findings from a phase III trial recently published in the <em>Journal of Clinical Oncology</em>.
Marcus E. Randall, MD
Marcus E. Randall, MD
Treatment with vaginal cuff brachytherapy plus paclitaxel and carboplatin chemotherapy (VCB/C) was not found to be superior to pelvic radiation therapy (RT) in patients with high-intermediate and high-risk early-stage endometrial cancer, according to findings from a phase III trial recently published in theJournal of Clinical Oncology.
The randomized trial also found that acute toxicity was greater with VCB/C and that late toxicity was similar between both arms, supporting the use of pelvic RT alone in these patient populations.
“Pelvic RT alone remains an effective, well-tolerated, and appropriate adjuvant treatment in high-risk early-stage endometrial carcinomas of all histologies,” wrote the investigators, led by Marcus E. Randall, MD, of the University of Kentucky.
The trial enrolled a total of 601 patients between 2009 and 2013 who were randomly assigned to receive either RT (n = 301) or VCB followed by intravenous paclitaxel at 175 mg/m2plus carboplatin every 21 days for 3 cycles (n = 300).
The median patient age was 63 and 74% had stage I disease. The majority of patients had endometrioid cancer (71%), and the remainder of patients had serous (15%) or clear cell (5%) histologies. The primary endpoint of the trial was recurrence-free survival (RFS). Secondary objectives included comparisons of overall survival (OS), patterns of failure, and frequency/severity of adverse events between the treatment arms.
Pelvic RT was administered using either standard 4-field techniques (3D conformal RT; 3D-CRT) or intensity-modulated RT (IMRT). Patients who received IMRT had treatment plans based on the Radiation Therapy Oncology Group Contouring Atlas. Pelvic RT was given at a dose of 45 to 50.4 Gy over 5 to 6 weeks (1.8 Gy per day for 25 to 28 fractions) and patients with cervical involvement or serous or clear cell histology were permitted to receive cuff brachytherapy boosts.
Patients assigned to VCB/C received cuff brachytherapy at a high-dose rate (6 to 7 Gy at 0.5-cm depth for 3 fractions, 10 to 10.5 Gy at the vaginal surface for 3 fractions, or 6 Gy at the vaginal surface for 5 fractions) or a low-dose rate (65 to 70 Gy prescribed at the vaginal surface in 1 to 2 insertions at a dose rate of 4 to 10 Gy per hour). Vaginal treatment length was not specified but was usually 3 to 5 cm. Chemotherapy was initiated up to 3 weeks from brachytherapy initiation.
Ninety-one percent of the 301 patients assigned to RT and 87% of the 300 patients assigned to VCB/C completed therapy, with recurrence rates on therapy of 0.3% and 1.3%, respectively. Thirty-two percent of patients who received RT also received brachytherapy.
At a median follow-up of 53 months, the 60-month RFS was 0.76 (95% CI, 0.70-0.81) for RT and 0.76 (95% CI, 0.70 to 0.81) for VCB/C (HR, 0.92; 90% CI, 0.69-1.23). The 60-month OS was 0.87 (95% CI, 0.83-0.91) for RT and 0.85 (95% CI, 0.81-0.90) for VCB/C (HR, 1.04; 90% CI, 0.71-1.52). Vaginal and distant recurrence rates were similar between the 2 arms, but pelvic and para-aortic nodal recurrences were more common in the VCB/C arm (9% vs 4%). The investigators did not find heterogeneity of treatment effect with RFS or OS among the variables evaluated.
“Assuming proportional hazards, the data are consistent with the hypothesis that the hazard of VCB/C is as much as 30% greater than that of RT alone. This effect size is comparable to increasing the probability of recurrence at 3 years by 5%,” the investigators wrote.
A total of 76 deaths were reported among the study participants. The investigators found the treatment hazard ratio for death was 1.04 (VCB/C vs pelvic RT;P= .57). They estimated 0.99, 0.93, and 0.91 of patients who received RT were alive at 12, 24, and 36 months, respectively, and 0.99, 0.93, and 0.88 of patients were alive in the VCB/C arm at the same time points.
At an interim analysis in 2013, investigators reported a primary RFS of 87 events at a median follow-up of 28 months. An updated analysis occurred at a median follow-up of 53 months, reporting 130 events, which included 16 patient deaths without known recurrence. Neither interim analysis resulted in the study being terminated.
“Pelvic RT remains an appropriate treatment for high-risk early-stage endometrial carcinoma. The benefit of adjuvant chemotherapy with regard to OS in stage I to II disease remains to be demonstrated in a prospective manner,” the investigators concluded.
Randall ME, Filiaci V, McMeekin S, et al. Phase III Trial: Adjuvant Pelvic Radiation Therapy Versus Vaginal Brachytherapy Plus Paclitaxel/Carboplatin in High-Intermediate and High-Risk Early Stage Endometrial Cancer. [published online April 17, 2019].J Clin Oncol. doi: 10.1200/JCO.18.01575.