Updated PORTEC-3 Analysis Shows Improved Survival With Chemoradiotherapy Versus Radiotherapy Alone

Greatest absolute benefit found in patients with stage III endometrial cancer or serous histology, or both

Updated survival outcomes of patients with high-risk endometrial cancer treated in the international randomised phase III PORTEC-3 study show that both, overall survival (OS) and failure-free survival (FFS) were significantly improved in women treated with combined adjuvant chemotherapy and radiotherapy compared with those treated with radiotherapy alone. The greatest absolute benefit was found for women with stage III or serous cancers, or both. In patients with a recurrence, the majority had distant metastases. Pelvic control was excellent in both groups. The results are published on 22 July 2019 in The Lancet Oncology. 

Patients with endometrial cancer generally have a favourable prognosis. Only 15–20% have high-risk disease defined as endometrioid endometrial cancer stage I, grade 3 with deep invasion, stage II or III endometrioid endometrial cancer with no residual disease, or non-endometrioid (serous or clear cell) histology.

Current standard of postoperative care in patients with high-risk endometrial cancer is pelvic external-beam radiotherapy. In previous adjuvant studies, a higher incidence of pelvic relapses has been reported with adjuvant chemotherapy alone compared with a treatment schedule that includes external-beam radiotherapy.

In PORTEC-3 study, the patients with high-risk disease were randomly assigned to receive pelvic radiotherapy alone or the combination of radiotherapy with two cycles of concurrent cisplatin followed by four cycles of adjuvant paclitaxel/carboplatin.

The study co-primary endpoints were OS and FFS. Secondary endpoints of vaginal, pelvic, and distant recurrence were analysed according to the first site of recurrence. Survival endpoints were analysed by intention-to-treat, and adjusted for stratification factors. Competing risk methods were used for FFS and recurrence.

The study team performed a post-hoc analysis to analyse patterns of recurrence with one additional year of follow-up. The study was closed on 20 December 2013 upon 686 participants have been enrolled, of whom 660 were eligible and evaluable (330 in each arm). Follow-up is ongoing.

At a median follow-up of 72.6 months, 5-year OS was 81.4% with chemoradiotherapy versus 76.1% with radiotherapy alone (adjusted hazard ratio [HR] 0.70, p = 0.034). The 5-year FFS was 76.5% versus 69.1% (HR 0.70, p = 0.016).

Distant metastases were the first site of recurrence in most patients with a relapse, occurring in 78 of 330 patients giving 5-year probability 21.4% in the chemoradiotherapy group versus 98 of 330 (5-year probability 29.1%) in the radiotherapy-alone group (HR 0.74; p = 0.047).

Isolated vaginal recurrence was the first site of recurrence in one patient (0.3%) in both groups.

Isolated pelvic recurrence was the first site of recurrence in three patients (0.9%) in the chemoradiotherapy group versus four (0.9%) in the radiotherapy-alone group.

At 5 years, only one grade 4 adverse event, in particular ileus or obstruction, was reported in the chemoradiotherapy group. At 5 years, reported grade 3 adverse events did not differ significantly between the two groups, occurring in 16 (8%) of 201 patients in the chemoradiotherapy group versus ten (5%) of 187 patients in the radiotherapy-alone group. The most common grade 3 adverse event was hypertension in four (2%) patients in both groups. At 5 years, grade 2 or worse adverse events were reported in 76 (38%) of 201 patients in the chemoradiotherapy group versus 43 (23%) of 187 patients in the radiotherapy-alone group (p = 0.002). Sensory neuropathy persisted more often after chemoradiotherapy than after radiotherapy alone, with 5-year rates of grade 2 or worse neuropathy of 6% (13 of 201 patients) versus 0% (0 of 187 patients). No treatment-related deaths were reported.

The authors concluded that combined adjuvant chemotherapy and radiotherapy should be discussed and recommended as a new standard of care, especially for women with stage III endometrial cancer or serous cancers, or both, as part of shared decision-making process. Follow-up is ongoing to evaluate long-term survival. Molecular studies on tissue samples from PORTEC-3 study participants are ongoing.

 

Reference

de Boer SM, Powell ME, Mileshkin L, et al. 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; Published online 22 July 2019. DOI: https://doi.org/10.1016/S1470-2045(19)30395-X.