Adjuvant chemoradiotherapy increases five-year overall survival and failure-free survival compared with radiotherapy alone for women with high-risk endometrial cancer, report the researchers of the phase 3 PORTEC-3 trial in their updated analysis, which has now been published in The Lancet Oncology.
Around 15% to 20% of patients with endometrial cancer are considered to have high-risk endometrial cancer, defined as endometrioid endometrial cancer stage 1, grade 3 with deep invasion; stage II or III endometrioid endometrial cancer, with no residual disease; or non-endometrioid cancer, with serous or clear cell histology.
PORTEC-3, an open-label trial led by the Dutch Gynaecological Oncology Group (DGOG) conducted at 103 centers by six clinical trial groups from the Netherlands, the United Kingdom, Australia and New Zealand, Italy, Canada, and France, enrolled 686 adult patients with high-risk endometrial cancer and a WHO performance status of 0 to 2, of whom 660 were eligible and evaluable for data analysis.
Patients were randomized in a 1:1 ratio to receive either radiotherapy alone, consisting of 48.6 Gy in 1.8 Gy fractions given on five days per week, or chemoradiotherapy, consisting of two cycles of cisplatin 50 mg/m2 administered intravenously during radiotherapy followed by four cycles of intravenous carboplatin AUC5 and paclitaxel 175 mg/m2.
In their previously reported efficacy results, published in March 2018, the authors of the PORTEC-3 trial found that after a median follow-up of 60.2 months, chemoradiotherapy produced a 7% improvement in five-year failure-free survival over radiotherapy alone, but it did not produce a statistically significant difference in five-year overall survival. The updated results after a median follow-up of 72.6 months now show increases in five-year overall survival (81.4% for chemoradiotherapy vs 76.1% for radiotherapy alone), as well as a continuance of higher five-year failure-free survival (76.5% vs 69.1%).
Distant metastases, which occurred in 21.4% of patients in the chemoradiotherapy arm and in 29.1% of patients in the radiotherapy-only arm over the course of five years, were the most common first site of recurrence for those who experienced a relapse. Subgroup analyses revealed that for patients with serous cancers, who had worse rates of overall survival and failure-free survival than did patients with other histological types, chemoradiotherapy increased overall survival by 19% and increased failure-free survival by 12% compared with radiotherapy alone.
At five years, only one grade 4 adverse event was reported—ileus or obstruction—in the chemoradiotherapy group. Grade 3 adverse events were similar between the two trial arms (8% vs 5%), the most frequent being hypertension, which occurred in 2% of women in both arms. Women in the chemoradiotherapy arm did experience higher rates of grade 2 or higher adverse events (38% vs 23%), including grade 2 or higher neuropathy (6% vs 0%).There were no treatment-related deaths.
"This updated analysis of the PORTEC-3 trial shows improved five-year overall and failure-free survival with chemoradiotherapy compared with radiotherapy alone for women with high-risk endometrial cancer, with the greatest absolute benefit for chemotherapy seen in women with stage III disease or serous cancers, or both," conclude the researchers, led by first author Stephanie M. de Boer, MD, a radiation oncologist at Leiden University Medical Centre, the Netherlands. "Most recurrences were at distant sites, suggesting that new systemic treatment approaches are needed to improve survival outcomes. Molecular analysis has the potential to improve risk stratification and should be used to identify subgroups that can derive the greatest benefit from chemotherapy and to select patients for targeted therapies; molecular studies on tissue samples donated by PORTEC-3 trial participants are ongoing."
For More Information
de Boer SM, Powell ME, Mileshkin L, et al (2019). Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol. [Epub ahead of print] DOI:10.1016/S1470-2045(19)30395-X
de Boer SM, Powell ME, Mileshkin L, et al (2018). 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, 19(3):295-309. DOI:10.1016/S1470-2045(18)30079-2
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