As reported in The Lancet Oncology by Stephanie de Boer, MD, and colleagues, a post hoc updated survival analysis of the phase III PORTEC-3 trial has shown a significant overall survival benefit of adjuvant chemoradiotherapy vs radiotherapy alone in women with high-risk endometrial cancer. A benefit in failure-free survival was maintained.
The open-label trial included 660 women from 103 sites within six clinical trial groups collaborating in the Gynecological Cancer Intergroup. Patients were randomly assigned between November 2006 and December 2013 to receive radiotherapy alone at 48.6 Gy in 1.8 Gy fractions 5 days per week (n = 330) or chemoradiotherapy with two cycles of cisplatin 50 mg/m² during radiotherapy followed by four cycles of carboplatin (AUC 5) and paclitaxel 175 mg/m² (n = 330). The coprimary endpoints were overall and failure-free survival.
At a median follow-up of 72.6 months, estimated 5-year overall survival was 81.4% in the chemoradiotherapy group vs 76.1% in the radiotherapy group (adjusted hazard ratio [HR] = 0.70, P = .034). The rates of 5-year failure-free survival were 76.5% vs 69.1% (HR = 0.70, P = .016).
In post hoc exploratory analyses, 5-year overall survival rates were 78.5% in the chemoradiotherapy group vs 68.5% in the radiotherapy group (HR = 0.63, P = .043), and 5-year failure-free survival rates were 70.9% vs 58.4% (HR = 0.61, P = .011) among women with stage III endometrial cancer. Among women with stage I or II disease, 5-year rates were 83.8% vs 82.0% (HR = 0.83, P = 0.45) for overall survival and 81.3% vs 77.3% for failure-free survival (HR = 0.86, P = .51). Among patients with serous cancers, 5-year rates were 71.4% vs 52.8% (HR = 0.48, P = .037) for overall survival and 59.7% vs 47.9% (HR = 0.42, P = .008) for failure-free survival.
Distant metastases constituted the first type of recurrence in 78 patients in the chemoradiotherapy group vs 98 in the radiotherapy group (5-year probability = 21.4% vs 29.1%, HR = 0.74, P = .047). Overall, distant metastases occurred in 80 vs 99 patients (5-year probability = 22.1% vs 29.4%, P = .057). Pelvic recurrence was observed in 20 vs 31 patients (5.5% vs 8.5%, HR = 0.63, P = 0.11) and vaginal recurrence was observed in eight vs eight patients (2.1% vs 2.1%, HR = 0.99, P = 0.99. Pelvic recurrence was the first recurrence in three vs four patients, and vaginal recurrence was the first recurrence in one patient in each group.
With additional follow-up, no significant differences between groups were observed in grade ≥ 3 adverse events at 12, 36, or 60 months after randomization. At 60 months, grade 3 adverse events were reported in 8% of 201 women in the chemoradiotherapy group vs 5% of 187 women in the radiotherapy group (P = .24).
The investigators concluded, “This updated analysis shows significantly improved overall survival and failure-free survival with chemoradiotherapy vs radiotherapy alone. This treatment schedule should be discussed and recommended especially for women with stage III or serous cancers, or both, as part of shared decision-making between doctors and patients.…” ■