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TOPLINE:

HER2DX, a standardized 27-gene expression test, appears to predict event-free survival in patients with early-stage HER2+ breast cancer, and the test could be used to identify candidates for less intensive treatment, a pooled data analysis suggested.

METHODOLOGY:

• Researchers conducted a patient-level meta-analysis of seven cohorts that had HER2DX risk scores as well as clinical and efficacy data available.
• They included three randomized clinical trials with a total of 722 patients, two single-arm trials with 368 patients, and two observational studies with 941 patients.
• Four of the studies involved neoadjuvant therapy (in a total of 803 patients), and three looked at adjuvant therapy (in a total of 1228 patients).
• The patients tended to have tumor stage T1 (49.5%) or T2 (29.0%) disease, with no nodal involvement (67.4%), and be hormone receptor–positive (65.7%). The majority (60.5%) received adjuvant therapy alone. Among those given neoadjuvant therapy, 42.5% had a pathologic complete response (pCR).
• The primary endpoint, assessed using Kaplan-Meier analysis, was event-free survival.

TAKEAWAY:

• Overall, 52.4% of patients were considered low-risk on the basis of their HER2DX score, while 47.6% were considered high-risk.
• Multivariate analysis showed that each 10-unit increment in HER2DX score was associated with a significant increase in event-free survival (hazard ratio [HR], 1.23; P < .001).
• The relationship remained significant when stratifying patients by tumor and nodal stage and by hormone receptor and pCR status, whether using HER2DX risk as a continuous score or dividing patients into high- vs low-risk groups.
• When applying risk groups to the overall study population, the team found that low-risk patients had a significant increase in event-free survival compared with high-risk patients (HR, 2.55; P < .001). At 6 years, 93% of patients in the low-risk group remained event-free compared with 82.9% in the high-risk group.

IN PRACTICE:

"In patients with early-stage HER2+ breast cancer, HER2DX provides prognostic information on long-term outcomes beyond classical variables," said study presenter Guillermo Villacampa, MD, Oncology Data Science, Vall d'Hebron Institute of Oncology, Barcelona, Spain. The test "can help to better identify patients who may benefit from less intensive treatment and those who could benefit from more aggressive approaches," he added.

SOURCE:

The research was presented at the ESMO Breast Cancer 2024 Annual Congress on May 16.

LIMITATIONS:

Session co-chair Thomas Bachelot, MD, PhD, head of the breast cancer and clinical trial units at Centre Leon Berard, Lyon, France, commented on several outstanding questions. These include whether the assay will help with dose de-escalation or intensification of newer drugs than those given in the studies used for the meta-analysis and whether using HER2DX is "more efficient" than dynamic treatment selection during the patient journey.

Moreover, it is not clear whether the assay will be "useful for selecting patients who don't need any adjuvant treatment." HER2DX also needs prospective validation, Bachelot said, and that data will be provided by the DEFINITIVE international prospective trial.

DISCLOSURES:

The research was funded by Reveal Genomics.

Villacampa declared relationships with AstraZeneca, Pfizer, MSD, GlaxoSmithKline, and Pierre Fabre.

Bachelot declared relationships with Roche, Novartis, Seagen, Pfizer, AstraZeneca/Daiichi, and Lilly.