Messaggi chiave
- EUROPA è uno studio multicentrico di fase III, randomizzato, di non inferiorità, disegnato per confrontare gli effetti della radioterapia (RT) rispetto alla terapia endocrina (ET) sugli esiti di qualità della vita correlata alla salute (HRQoL) e recidiva tumorale ipsilaterale in donne anziane con carcinoma mammario precoce a basso rischio sottoposte a chirurgia conservativa. Si presentano di seguito i risultati di un’analisi ad interim prepianificata.
- L’analisi è stata condotta su un totale di 104 pazienti nel gruppo RT e 103 nel gruppo ET. A un follow-up mediano di 24 mesi, la variazione media rispetto al basale nel punteggio sulla scala dello stato di salute globale del questionario EORTC QLQ-C30 è risultata pari a -3,40 nel gruppo RT e a -9,79 nel gruppo ET, con una differenza media aggiustata di 6,39 (0,14-12,65; p = 0,045) a favore della RT. L’incidenza di eventi avversi (EA) correlati al trattamento è stata inferiore nelle pazienti sottoposte a RT (67%) rispetto al gruppo ET (85%). Gli EA G3-4 più comuni sono stati artralgia (0 vs 7%), prolasso degli organi pelvici (0 vs 3%), affaticamento, vampate di calore, mialgia, dolore osseo e fratture (0 vs 2% per ciascun evento). EA seri sono stati segnalati nel 15% delle pazienti di entrambi i gruppi, mentre non vi sono stati casi di decesso correlato al trattamento.
- In questa analisi, l’ET è stata associata a una riduzione maggiore della HRQoL rispetto alla RT nella valutazione a 2 anni. Sebbene questi risultati suggeriscano una potenziale superiorità della RT in termini di mantenimento della qualità della vita, si dovranno attendere i dati relativi agli esiti di controllo della malattia prima di trarre conclusioni definitive.
Abstract
Background
- Optimal therapy following breast-conserving surgery in older adults with low-risk, early-stage breast cancer remains uncertain.
- The EUROPA trial aims to compare the effects of radiotherapy and endocrine therapy as single-modality treatments on health-related quality of life (HRQOL) and ipsilateral breast tumour recurrence (IBTR) outcomes in this population.
Methods
- This non-inferiority, phase 3, randomised study was conducted at 18 academic hospitals across Italy (17 centres) and Slovenia (one centre).
- Eligible patients were women aged 70 years or older with histologically confirmed, stage I, luminal A-like breast cancer, who had undergone breast-conserving surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1.
- Patients were randomly assigned (1:1) to receive single-modality endocrine therapy or radiotherapy.
- Endocrine therapy consisted of daily oral aromatase inhibitors or tamoxifen, for a total planned duration of 5-10 years as per clinical discretion, while radiotherapy was administered as either whole breast or partial breast irradiation, delivered in 5-15 fractions.
- Randomisation was stratified by health status according to the Geriatric 8 (G8) screening tool and by age, with allocation concealed and no blinding.
- The co-primary endpoints were the change in HRQOL, assessed by the global health status (GHS) scale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item core module at 24 months, and 5-year IBTR rates (not reported here).
- This preplanned interim analysis was performed once at least 152 patients completed the 24-month GHS HRQOL assessment.
- The safety population comprised patients who received the study intervention at least once after randomisation.
- The study is registered with ClinicalTrials.gov, NCT04134598, and is ongoing and actively recruiting.
Findings
- Between March 4, 2021, and June 14, 2024, 731 women were randomly assigned to receive radiotherapy (n = 365) or endocrine therapy (n = 366).
- This analysis included 104 patients in the radiotherapy group and 103 in the endocrine therapy group, with a median follow-up of 23·9 months (IQR 22·9-24·2).
- Patients were predominantly White (204 [99%] of 207) and the median age was 75·0 years (IQR 73·0-80·0) in the radiotherapy group and 74·0 years (72·0-80·0) in the endocrine therapy group.
- 86 patients in the radiotherapy group and 75 in the endocrine therapy group completed the 24-month HRQOL assessment.
- The mean baseline GHS score was 71·9 (SD 19·1) in the radiotherapy group and 75·5 (19·3) in the endocrine therapy group.
- At 24 months, the age-adjusted, G8 score-adjusted mean change from baseline in GHS was -3·40 (95% CI -7·82 to 1·03; p = 0·13) in the radiotherapy group and -9·79 (-14·45 to -5·13; p <0·0001) in the endocrine therapy group, with an adjusted mean difference of 6·39 (0·14 to 12·65; p = 0·045) favouring radiotherapy.
- Treatment-related adverse events were less frequent in the radiotherapy group (65 [67%] of 97 patients) compared with the endocrine therapy group (76 [85%] of 89).
- The most common grade 3-4 adverse events were arthralgia (six [7%] of 89 in the endocrine therapy group vs 0 of 97 in the radiotherapy group), pelvic organ prolapse (three [3%] vs 0), fatigue, hot flashes, myalgia, bone pain, and fractures (two [2%] vs 0 for each).
- Serious adverse events were reported in 15 (15%) patients in the radiotherapy group and 13 (15%) in the endocrine therapy group.
- There were no treatment-related deaths in either group.
Interpretation
- Endocrine therapy was associated with a greater reduction in HRQOL, as measured by GHS, compared with radiotherapy at 24 months.
- While these interim results suggest radiotherapy might better preserve HRQOL in older women with low-risk early breast cancer, further data on disease control outcomes and final patient accrual are needed to draw definitive conclusions.