August 05, 2019
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Chemoradiotherapy improves survival in high-risk endometrial cancer

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Chemoradiotherapy significantly improved OS and failure-free survival compared with pelvic radiotherapy alone among women with high-risk endometrial cancer, according to results from the PORTEC-3 randomized phase 3 trial published in The Lancet Oncology.

“Previously reported efficacy results with a time-based analysis and median follow-up of 60.3 months showed a significant 7% improvement in failure-free survival for patients treated with chemoradiotherapy compared with those treated with radiotherapy alone, without a significant difference in overall survival,” Stephanie M. de Boer, MD, of the department of radiation oncology at Leiden University Medical Center in the Netherlands, and colleagues wrote. “The aim of the present analysis of the PORTEC-3 trial is to present the patterns of recurrence, treatment and survival after recurrence and an updated analysis of the primary endpoints with prolonged follow-up.”

The open-label, multicenter, phase 3 trial led by the Dutch Gynecological Oncology group included 660 women with high-risk endometrial cancer enrolled between Nov. 23, 2007, and Dec. 20, 2013. All women had International Federation of Gynecology and Obstetrics 2009 stage I endometrioid grade 3 cancer with deep myometrial invasion, lymphovascular space invasion or both; stage II or stage III disease; or stage I to stage III disease with clear cell or serous histology. All had previously undergone surgery, which consisted of total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy.

Researchers randomly assigned participants 1:1 to receive radiotherapy alone (48.6 Gy in 1.8 Gy fractions 5 days per week; n = 330; median age, 62 years) or chemoradiotherapy (two cycles of IV cisplatin 50 mg/m2 during radiotherapy, followed by four cycles of IV carboplatin with an area under the curve of 5 and IV paclitaxel 175 mg/m2; n = 330; median age, 62.4 years). They used a biased coin minimization procedure to ensure balance between groups, with stratification for participating site, lymphadenectomy, stage and histological type.

OS and failure-free survival served as co-primary endpoints. Secondary endpoints included vaginal, pelvic and distant recurrence, assessed according to first location of recurrence.

At median follow-up of 72.6 months (interquartile range, 59.9-85.6), results showed a 5-year OS rate of 81.4% (95% CI, 77.2-85.8) with chemoradiotherapy vs. 76.1% (95% CI, 71.6-80.9) with radiotherapy alone (adjusted HR [aHR] = 0.7; 95% CI. 0.51-0.97).

Rates of 5-year failure-free survival were 76.5% (95% CI, 71.5-80.7) with chemoradiotherapy vs. 69.1% (95% CI, 63.8-73.8) with radiotherapy alone (aHR = 0.7; 95% CI, 0.52-0.94).

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Most women who relapsed experienced distant metastases as the first site of recurrence, including 78 women in the chemoradiotherapy group (5-year probability, 21.4%; 95% CI, 17.3-26.3) and 98 women in the radiotherapy-alone group (5-year probability, 29.1%; 95% CI, 24.4-34.3; HR = 0.74; 95% CI, 0.55-0.99). These included one woman in each group (0.3%; 95% CI, 0.9-2.1) with isolated vaginal recurrence, and three women in the chemoradiotherapy group and four women in the radiotherapy-alone group with isolated pelvic recurrence (HR = 0.75; 95% CI, 0.17-3.33).

By 5-year follow-up, only one grade 4 adverse event — ileus — had been documented, in the chemoradiotherapy group. Researchers observed no significant difference in rates of grade 3 adverse events between the groups at 5 years (8% chemoradiotherapy vs. 5% radiotherapy-alone). Hypertension was the most prevalent grade 3 adverse event, occurring among four women in each group.

Rates of grade 2 or worse adverse events differed significantly between the groups at 5 years (38% vs. 23%; P = .002), including persistent sensory neuropathy in the chemoradiotherapy group (6% vs. 0%). No deaths associated with treatment were documented.

These findings represent another step forward in adjuvant treatment of advanced endometrial cancer, but the many variations in the disease continue to hinder large randomized trials, according to a related editorial by Marcus E. Randall, MD, chair of the department of radiation medicine at University of Kentucky.

“Based on outstanding work done by the PORTEC Study Group and others, we have made good progress in improving outcomes for women with high-risk and locally advanced endometrial cancers,” Randall wrote. “However, we are not there yet.” – by Jennifer Byrne

Disclosures: de Boer reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Randall reports honoraria from IsoRay Medical.