EUROPA Trial

Design - Phase 3 academic randomized trial: postoperative radiotherapy alone vs adjuvant endocrine therapy alone, women >=70y with stage I luminal A-like BC after breast-conserving surgery (NCT04134598).

HRQoL (co-primary, 24 mo) - Global health status better preserved with radiotherapy: adjusted mean change -3.4 (RT) vs -9.79 (endocrine therapy); between-arm difference favored RT (GHS difference reported 6.39, P=0.045).

Recurrence / OS - At 24 months, no ipsilateral breast tumor recurrence, locoregional relapse, or breast-cancer deaths in either arm; deaths during follow-up (4 RT, 2 ET) were not breast-cancer related. 5-year IBTR co-primary endpoint pending.

Safety - Grade >=3 adverse events 67.0% (RT) vs 85.4% (endocrine therapy); discontinuation due to AEs 0% (RT) vs 12.4% (ET).

Regulatory - Investigational/academic single-modality de-escalation strategy; not an FDA drug-registration trial.

Sponsor - Fondazione Radioterapia Oncologica / Careggi (Italian academic consortium).

Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated July 21, 2026.

HRQOL (Global Health Status) at 24 months + 5-year IBTR — Co-Primary Endpoints

Median: -3.4 ΔGHS from baseline (radiotherapy alone) vs. -9.79 ΔGHS from baseline (endocrine therapy alone). GHS change RT arm rate: -3.4% (adjusted mean Δ) vs. -7.82 to 1.03% (95% CI). GHS change ET arm rate: -9.79% (adjusted mean Δ) vs. -14.45 to -5.13% (95% CI). Adjusted mean difference rate: 6.39% (favoring RT) vs. 0.14-12.65% (95% CI). Phase 3 non-inferiority trial (N=731 randomized; interim analysis N=207 with median follow-up 23.9 months). Co-primary 1 (HRQOL): adjusted mean change in Global Health Status at 24 months was -3.40 (95% CI -7.82 to 1.03, P=0.13) with RT vs. -9.79 (95% CI -14.45 to -5.13, P<0.0001) with ET — adjusted mean difference 6.39 (95% CI 0.14-12.65, P=0.045) FAVORING RADIOTHERAPY. Co-primary 2 (5-year IBTR): NOT reported at interim. Meattini et al., Lancet Oncol 2025;26(1):37-50.

Overall Survival (OS)

At 24 months: NO ipsilateral breast tumor recurrence (IBTR), locoregional relapse, or breast cancer-related deaths in either arm. 5-year IBTR co-primary endpoint pending. 4 patients in RT arm and 2 in ET arm died during follow-up; none were breast cancer-related. Final analysis scheduled at 5 years.

Safety & Tolerability

Grade ≥3 adverse events: 67.0% (rt) vs. 85.4% (et). Discontinuation due to AEs: 0% (rt) vs. 12.4% (et). Key AEs: RT arm: arthralgia (28.9%), fatigue (33.0%), breast pain (38.1%), bone pain (23.7%), ET arm: arthralgia (69.7%), fatigue (44.9%), hot flashes (32.6%), myalgia (31.5%), bone pain (28.1%), alopecia (25.8%), ET arm Grade ≥3: arthralgia (7%), pelvic organ prolapse (3%). Treatment-related AE rates 67.0% (RT) vs. 85.4% (ET), adjusted difference -18.4 (95% CI -30.2 to -6.2). Within 24 months, 22.5% of ET patients switched to different treatment, 12.4% discontinued ET entirely. Serious AEs 15% vs. 15%. Both arms had 2 fatal TEAEs: RT (esophageal neoplasia, Listeria meningitis); ET (pneumonia, ischemic heart disease). 84.6% of RT patients received partial breast irradiation (5-8 fractions), 15.4% received whole-breast RT.

Clinical Implications

🔄 Interim: radiotherapy better preserves QOL vs. endocrine therapy in 70+ luminal A BC; 5-year IBTR still awaited. EUROPA challenges the assumption that ET is superior to RT as single-modality post-breast-conserving surgery in low-risk older women. At 24 months, RT preserved HRQOL significantly better than ET (adjusted difference 6.39, P=0.045), with substantially lower AE burden (67% vs. 85%) and lower discontinuation. ET was associated with a 22.5% treatment switch rate and 12.4% discontinuation. Both single-modality options showed zero IBTR/relapse/BC-death at 24 months — definitive 5-year IBTR data needed to confirm equivalent disease control. Supports ultra-hypofractionated partial-breast RT (5 fractions) as practical alternative to 5-10 years of daily AI/tamoxifen in elderly patients. Discussant noted PRIME II and CALGB 9343 suggest RT omission is also reasonable.

What is the EUROPA trial?

EUROPA (NCT04134598) is a Phase 3, academic randomized trial from an Italian consortium (Fondazione Radioterapia Oncologica / Careggi) comparing exclusive postoperative radiotherapy alone versus exclusive adjuvant endocrine therapy alone in women aged 70 years or older with stage I luminal A-like early breast cancer after breast-conserving surgery. Its co-primary endpoints are quality of life at 24 months and 5-year ipsilateral breast tumor recurrence.

What did EUROPA show at the interim analysis?

At 24 months, radiotherapy alone better preserved global health status/quality of life than endocrine therapy alone (adjusted mean change -3.4 versus -9.79). There were no ipsilateral breast tumor recurrences, locoregional relapses, or breast-cancer deaths in either arm at 24 months. The 5-year ipsilateral breast tumor recurrence co-primary endpoint is still awaited.

Is EUROPA testing a new drug?

No. EUROPA is a de-escalation strategy trial that compares two single-treatment approaches - radiotherapy alone versus endocrine therapy alone - after breast-conserving surgery in older women with low-risk disease. It is not an FDA drug-registration study and does not evaluate a new medicine for approval.

How did side effects compare between radiotherapy and endocrine therapy?

Grade 3 or higher adverse events were less frequent with radiotherapy (67.0%) than with endocrine therapy (85.4%), and no patients discontinued radiotherapy due to adverse events versus 12.4% discontinuing endocrine therapy. Endocrine therapy was associated with more arthralgia, fatigue, hot flashes and myalgia.

Why does EUROPA matter for older women with breast cancer?

EUROPA challenges the assumption that endocrine therapy is preferable to radiotherapy as single-modality treatment after breast-conserving surgery in low-risk older women. Its interim data suggest radiotherapy alone can better preserve quality of life, though the 5-year local recurrence result is needed before firm conclusions.