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Benefit of chemo + RT for high-risk endometrial cancer increases with time

Key clinical point: Adjuvant chemoradiotherapy has better long-term efficacy than radiotherapy alone for high-risk endometrial cancer.

Major finding: With a median follow-up of about 6 years, patients treated with chemoradiotherapy still had significantly better 5-year failure-free survival (HR for events, 0.70; P = .016) and now had significantly better 5-year overall survival (HR for death, 0.70; P = .034).

Study details: Updated analysis of an open-label, multicenter phase 3 randomized controlled trial among 660 women with high-risk endometrial cancer (POR-TEC-3 trial).

Disclosures: Dr. de Boer disclosed no competing interests in relation to the study. The study was supported in part by the Dutch Cancer Society, Cancer Research UK, National Health and Medical Research Council, Cancer Australia, the Italian Medicines Agency, and the Canadian Cancer Society Research Institute.

Citation:

de Boer SM et al. Lancet Oncol. 2019 Jul 22. doi: 10.1016/S1470-2045(19)30395-X.

Commentary:

Results of PORTEC-3 are potentially practice changing but generate several questions relevant to optimizing adjuvant therapy for high-risk endometrial cancer, Marcus Randall, MD, contends in a commentary (Lancet Oncol. 2019 Jul 22. doi: 10.1016/S1470-2045[19]30416-4).

One question is applicability of the findings across trial subgroups, which is still uncertain. “However, taking into account the statistical limitations of subgroup analyses, the therapeutic benefit of combined chemotherapy and radiotherapy (vs. radiotherapy alone) appeared to remain confined to patients with stage III disease and those with serous carcinomas of all stages,” he noted.

Another question is whether chemotherapy alone is sufficient. Here, results from trials conducted by the Gynecologic Oncology Group (now NRG Oncology) suggest that omitting pelvic radiotherapy increases the risk of locoregional failure, according to Dr. Randall.

A final question is whether there is a preferred approach for combining chemotherapy with radiotherapy. “Increasing evidence supports the use of upfront systemic therapy, when combined with radiotherapy, as a strategy to maximise both systemic and local control. ... Many clinicians often use this regimen as a preferred adjuvant approach in locally advanced endometrial cancer,” he noted.

“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. However, we are not there yet,” Dr. Randall concludes.

Marcus Randall, MD, is with the department of radiation medicine, University of Kentucky, Lexington. He has no disclosures related to the commentary.