medwireNews: Adding chemotherapy during and after radiotherapy may benefit some women with stage III endometrial cancer, indicate findings from the PORTEC-3 trial.
Adjuvant chemoradiotherapy significantly improved 5-year failure-free survival (FFS) rates, compared with radiotherapy alone, in 660 women with high-risk endometrial cancer, according to FIGO staging criteria.
This difference was mainly driven by an 11% absolute improvement with adjuvant chemoradiotherapy over radiotherapy alone in a subgroup of 295 women with stage III endometrial cancer, the team notes. The improvement was deemed “clinically relevant” having exceeded the 10% improvement used to design the study.
For the 365 women with stage I–II endometrial cancer, however, there was no significant improvement in FFS with chemoradiotherapy, and there was no overall survival benefit with adjuvant treatment for the group as a whole or for either subgroup.
The team, led by Stephanie de Boer (Leiden University Medical Center, the Netherlands), explains that “[p]atients with stage III cancer had the greatest benefit with chemoradiotherapy because of their higher risk of disease recurrence; for these patients, combined treatment should be considered to maximize failure-free survival.”
But they add: “Combined adjuvant chemotherapy and radiotherapy cannot be recommended as a new standard of care for patients with stage I–II endometrial cancer because no survival differences were found and pelvic control was high with radiotherapy.”
For the randomized trial, reported in The Lancet Oncology, 330 women received a total radiotherapy dose of 48.6 Gy, given in 1.8 Gy fractions on 5 days per week, while 330 received radiotherapy plus two cycles of cisplatin during radiotherapy and four cycles of carboplatin and paclitaxel afterwards.
The authors should be applauded for their design and completion of this large prospective trial.
Click for an expert comment by Ramez Eskander
The 5-year FFS rates were 75.5% with chemoradiotherapy versus 68.6% with radiotherapy alone, giving a significant hazard ratio (HR) of 0.71 after taking into account stratification factors including type of surgery, disease stage, and histological type.
The overall survival rates were a corresponding 81.8% and 76.7%, with a nonsignificant HR of 0.76.
Stratification by stage showed that women with stage III endometrial cancer benefitted most from chemoradiotherapy, with a 5-year FFS of 69.3%, which was significantly better than the 58.0% rate for stage III women receiving radiotherapy alone (HR=0.66).
Pelvic control was good for women receiving chemoradiotherapy or radiotherapy. Isolated recurrences were rare affecting just three and five patients in each group, respectively, and the 5-year rates for isolated and combined pelvic recurrences as well as distant recurrences were estimated to be 4.9% with chemoradiotherapy versus 9.2% with radiotherapy.
While the researchers recommend combined treatment for women with stage III endometrial cancer to improve FFS, they caution that this improvement “should be weighed against the severity and duration of toxicity of combined treatment, especially since overall survival was not significantly improved.”
They found that significantly more patients receiving chemoradiotherapy had grade 3 or worse adverse events, primarily hematological in nature, over the median 60.2 months of follow-up than did those receiving radiotherapy, at 60% versus 12%. The difference was significant at 6 months, with rates of 16% versus 8%, respectively, but from 12 months onwards the rates were similar.
The most significant and clinically relevant difference was in grade 2 or worse sensory neuropathy, which persisted for 5 years in 9% of women receiving chemoradiotherapy but in none of the women receiving radiotherapy.
In a related commentary, Sean Dowdy and Gretchen Glaser, both from Mayo Clinic, Rochester in Minnesota, USA, agree that for stage III patients, the improvement in FFS “seems to justify” the accompanying toxicity.
“Future trials should investigate regimens to maximize the local control advantages of radiotherapy with distant control improvements seen with chemotherapy for patients with high-risk endometrial cancer,” they write.
“Continued assessment of toxicity, quality of life, and cost will be paramount to define optimal adjuvant therapy.”
By Lucy Piper
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