In a European phase III trial (PORTEC-4a) reported in The Lancet Oncology, van den Heerik et al found that molecular profile–based adjuvant treatment produced favorable results in women with high-intermediate risk endometrial cancer and allowed patients with favorable risk to be spared adjuvant treatment.
Study Details
In the open-label trial, 564 patients from sites in eight European countries were randomly assigned 2:1 between June 2016 and December 2021 to a molecular profile group (n = 367) or a standard group (n = 197). In the molecular profile group, adjuvant treatment was observation in those with a favorable risk profile; brachytherapy (21 Gy in three fractions of 7 Gy given at 5–7 day intervals) in those with an intermediate profile; and pelvic radiotherapy (45.0–48.6 Gy in 1.8–2.0 Gy fractions, 5 days per week) in those with an unfavorable profile. The standard group received standard brachytherapy. The primary endpoint of the study was 5-year cumulative incidence of vaginal recurrence as first event.
Key Findings
Median follow-up was 58.1 months (interquartile range = 40.7–63.6 months). In the molecular profile group, 46% of patients had a favorable risk profile, 40% had an intermediate risk profile, and 14% had an unfavorable risk profile. In the standard group, 55% had a favorable risk profile, 33% had an intermediate risk profile, and 12% had an unfavorable risk profile.
Among all patients, the 5-year cumulative incidence of vaginal recurrence was 4.5% (95% confidence interval [CI] = 2.23%–6.76%) in the molecular profile group vs 1.6% (95% CI = 0.00%–3.32%) in the standard group (hazard ratio [HR] = 2.71, 95% CI = 0.79–9.34); the upper bound of the one-sided confidence interval of the difference (5.3%) was below the predefined-equivalence margin of 7.0% (P for noninferiority = .005).
The 5-year cumulative incidence of vaginal recurrence for the molecular profile group patients vs the standard group patients with favorable risk was 4.1% vs 0.9% (HR = 3.97, 95% CI = 0.48–32.95).
Adverse events were primarily grade 1 to 2. Grade 3 or worse treatment-related genitourinary toxicities occurred in four patients (1%) in the molecular profile group and four (2%) in the standard group. One serious adverse event was considered possibly related to treatment, consisting of vaginal scar dehiscence in a patient in the standard group. No treatment-related deaths were reported.
The investigators concluded: “Individualized adjuvant treatment by molecular integrated risk profile is safe and effective for patients with high-intermediate risk endometrial cancer; it spared 46% of patients with a favorable profile from adjuvant treatment, and reduces both overtreatment and undertreatment.”
Anne-Sophie van den Heerik, MD, of Leiden University Medical Centre, Leiden, Netherlands, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by KWF Dutch Cancer Society. For full disclosures of the study authors, visit thelancet.com.
