Better HRQOL With Radiotherapy for 70+ with Early Breast Cancer

SAN ANTONIO — Women 70 years or older with early luminal A-like breast cancer who received postoperative radiotherapy alone following surgery reported having better health-related quality of life at 24 months of follow-up than their peers who received only adjuvant endocrine therapy.

These findings come from a planned interim analysis of the phase 3 randomized EUROPA trial, in which older women with early-stage, favorable risk disease were assigned to either radiation alone or endocrine therapy following definitive surgery.

The analysis, conducted after 152 of the 926 planned patients enrolled had reached the 2-year mark, showed no major detriments in health-related quality of life measures with radiotherapy, whereas endocrine therapy was associated with a greater decline in most functional and symptomatic domains on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, reported Icro Meattini, MD, from the University of Florence, Florence, Italy.

Despite the findings tipping the scales in favor of radiotherapy, there are many factors that need to be considered when planning treatment, Meattini said.

“A take home message, really, really important: Radiotherapy or endocrine therapy may be a suitable, viable single-modality treatment option. We are accumulating data, so we should always emphasize the need for true multidisciplinary and true patient-centered personalized care,” he said in oral abstract presentation at San Antonio Breast Cancer Symposium (SABCS) 2024.

The study was also published online, in The Lancet Oncology, to coincide with the presentation.

High Prevalence of Lower-Risk Disease

There is a high prevalence of estrogen receptor-positive stage 1 breast cancer among women aged 70 years or older, and it’s important in this population to reduce the burden of treatment while balancing treatment efficacy with health-related quality of life, he said.

In previous studies that looked at omitting radiation there was an increase in local recurrence rates, and in studies of endocrine therapy, side effects as well as issues of drug adherence and/or persistence have been problematic, Meattini noted.

The multinational EUROPA trial was designed to directly compare ipsilateral breast tumor recurrence rates and health-related quality of life outcomes associated with single-modality radiation therapy vs endocrine therapy. The final analysis is scheduled to be conducted after all patients have been participating in the study for 5 years.

Interim Analysis Details

A total of 731 patients were enrolled from March 2021 through June 2024, and after stratification by age category (70-79 years vs 80 years or older) and score on the G8 geriatric screening tool, patients were randomly assigned on a 1:1 basis to endocrine therapy or radiotherapy. Endocrine therapy consisted of daily oral aromatase inhibitors or tamoxifen for a total planned duration of 5-10 years at the discretion of the prescribing clinician.

Radiotherapy was administered as either whole or partial breast irradiation. Meattini said that approximately 85% of the patients received partial breast irradiation, and that most of these treatments were ultra-hypofractionated, delivered over 5 consecutive days rather than the 15 fractions delivered over 3 weeks required for standard fractionated radiation.

The interim analysis included data on 104 patients assigned to radiotherapy and 103 assigned to endocrine therapy.

The primary endpoint, a change in mean global health status (GHS) score from baseline, favored the radiotherapy group. The mean baseline GHS score was 71.9 (out of a possible 100) in the radiotherapy group and 75.5 in the endocrine therapy group. At 24 months, the mean change from baseline, adjusted for age and G8 score, was −3.40 points in the radiotherapy group vs −9.79 in the endocrine therapy group, with an adjusted mean difference of 6.39 in favor of radiotherapy (P = .045).

Radiotherapy appeared to be easier to take, based on patient reported symptom scales and functional scales. In all, 67% of patients assigned to radiation had at least one treatment-related adverse event compared with 85% of patients assigned to endocrine therapy.

The most common grade 3-4 adverse events included arthralgia, which occurred in six patients assigned to endocrine therapy vs none assigned to radiotherapy; pelvic organ prolapse in three patients vs none; and fatigue, hot flashes, myalgia, bone pain, and fractures, each of which occurred in two patients vs none.

In the first 24 months of the study, there were no ipsilateral breast recurrences or locoregional recurrences in either study group. Two patients in the radiotherapy group and one in the endocrine therapy group were diagnosed with a contralateral breast tumor during follow-up, but there were no cases of distant metastases.

Four patients in the radiotherapy group and two in the endocrine therapy group died during follow-up, but none of the deaths was breast cancer–related, the investigators said.

Joint Decision-Making Essential

Elinor Sawyer, MBBS, PhD, from King’s College London, in London, England, the invited discussant, commented that there is now good evidence that partial breast irradiation is noninferior to whole-breast irradiation in this patient population, and that ultra-hypofractionation, with 26 Gy delivered over 5 fractions, is noninferior to 40 Gy delivered over 15 fractions.

“We all know that adherence to endocrine therapy is very variable and can decrease over time. And what we often find in the clinic is that we make a joint decision with the patient that we’re going to omit the radiotherapy, and then the patient returns to clinic 3 or 4 months later finding that they don’t tolerate their endocrine therapy, and we’ve kind of missed the opportunity to give the radiotherapy,” she commented.

Sawyer said she was hopeful that short-course radiotherapy could be a good alternative to offer patients and thinks “it’s really important that when we talk with patients that we explain the toxicities of both treatments, especially with the endocrine therapy, explain that some patients will get prolonged side effects.”

This study was funded by Fondazione Radioterapia Oncologica. Meattini disclosed receiving fees for advisory board participation supported by Eli Lilly, Novartis, Pfizer, AstraZeneca, Daiichi Sankyo, Gilead, and Menarini StemLine outside the EUROPA study. Sawyer disclosed receiving grant/research support from Pfizer, Seagen, and IQIVIA.

Neil Osterweil, an award-winning medical journalist, is a long-standing and frequent contributor to Medscape Medical News.