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Adjuvant Chemoradiotherapy May Be An Option For Certain High-Risk Endometrial Cancer Patients

Phase III trial results suggest that the failure-free survival benefit of adjuvant chemoradiotherapy is restricted to women with high-risk stage III endometrial cancer
14 Feb 2018
Anticancer Agents;  Endometrial Cancer;  Surgical Oncology;  Therapy;  Biological Therapy;  Radiation Oncology
By Shreeya Nanda, Senior medwireNews Reporter

medwireNews: Analysis of the primary endpoints of the PORTEC-3 trial suggests that adding chemotherapy during and after radiotherapy could benefit some patients with high-risk endometrial cancer. 

As reported in The Lancet Oncology, the chemoradiotherapy regimen significantly prolonged failure-free survival (FFS), but not overall survival (OS), in the total intention-to-treat population, with a clinically significant improvement in FFS observed in the subgroup of women with stage III disease. 

Given the lack of an OS difference and good pelvic control with radiotherapy alone, the researchers do not recommend the combined regimen for women with stage I–II cancer. They write that the modest FFS improvements with chemoradiotherapy seem “not to outweigh the cost in terms of toxicity and quality-of-life impairment”, which has been reported previously. 

However, the authors believe that chemoradiotherapy could be considered for stage III patients, who have a high risk of recurrence. 

Nonetheless, they stress that “the benefits and risks should be discussed for each individual patient.” 

The phase III trial enrolled 660 women considered to have high-risk disease as per the International Federation of Gynecology and Obstetrics classification, and randomly assigned them to receive a total radiotherapy dose of 48.6 Gy – given in 1.8 Gy fractions five days a week – either with or without two concomitant cycles of cisplatin plus four adjuvant cycles of carboplatin and paclitaxel. 

The 5-year FFS rate was 75.5% for the 330 participants who received chemoradiotherapy and 68.6% for the 330 given radiotherapy alone, a significant difference giving a hazard ratio (HR) of 0.71 after adjustment for factors such as stage and histology. 

The corresponding 5-year OS rates were 81.8% and 76.7%, and equated to a nonsignificant adjusted HR of 0.76. 

Lead author Stephanie de Boer, from Leiden University Medical Center in the Netherlands, and team note that pelvic control was good in both arms, with a low incidence of pelvic recurrences on study – in three patients in the chemoradiotherapy group and five in the radiotherapy group – and 5-year estimates of 4.9% and 9.2%, respectively. 

Stratification by stage showed that women with stage III endometrial cancer appeared to derive the greatest FFS benefit from chemoradiotherapy, with 5-year rates of 69.3% versus 58.0% for those given radiotherapy alone (HR=0.66). 

The authors point out that this absolute improvement of 11% “is clinically relevant and exceeds the 10% improvement used when designing the study.” 

Over a median follow-up of 60.2 months, 60% of patients in the chemoradiotherapy arm experienced adverse events of grade 3 or worse, which was significantly higher than the 12% rate observed in the radiotherapy arm. The difference was also significant at 6 months after randomisation, with respective rates of 16% and 8%, but the groups were comparable from 12 months onwards. 

Grade 2 sensory neuropathy, however, “persisted significantly more often” among women given chemoradiotherapy, with 8% reporting the side effect at the 5-year mark versus none of those who underwent radiotherapy alone, say Stephanie de Boer and colleagues. 

In a linked piece, commentators Sean Dowdy and Gretchen Glaser, both from Mayo Clinic in Rochester, Minnesota, USA, write: “Future trials should investigate regimens to maximise the local control advantages of radiotherapy with distant control improvements seen with chemotherapy for patients with high-risk endometrial cancer. 

“Continued assessment of toxicity, quality of life, and cost will be paramount to define optimal adjuvant therapy.” 

References 

de Boer SM, Powell ME, Mileshkin L, et al. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol; Advance online publication 12 February 2018. doi: http://dx.doi.org/10.1016/S1470-2045(18)30079-2  

Dowdy SC, Glaser GE. Adjuvant therapy for women with high-risk endometrial carcinoma. Lancet Oncol; Advance online publication 12 February 2018. doi: http://dx.doi.org/10.1016/S1470-2045(18)30091-3

Last update: 14 Feb 2018

medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group 

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