The ATTAIN trial, a Phase III study, is currently underway to evaluate the efficacy and safety of etirinotecan pegol in patients with advanced breast cancer who have developed brain metastases. This randomized trial compares etirinotecan pegol to the treatment of physician's choice (TPC) in patients with stable, treated breast cancer brain metastases who have previously been treated with an anthracycline, taxane, and capecitabine. The study addresses a significant clinical challenge, as the incidence of brain metastases in breast cancer is increasing, and treatment options remain limited.
Rationale for Etirinotecan Pegol
Etirinotecan pegol is a long-acting topoisomerase-1 inhibitor engineered to preferentially accumulate in tumor tissue, including brain metastases. This accumulation is designed to provide sustained cytotoxic levels of SN38, the active metabolite of irinotecan, directly within the tumor microenvironment. The rationale for this approach stems from the poor prognosis associated with breast cancer brain metastases and the need for therapies that can effectively target these lesions.
Trial Design and Endpoints
The ATTAIN trial (NCT02915744) is a Phase III, randomized study. Eligible patients must have stable, treated brain metastases from breast cancer and have received prior treatment with anthracyclines, taxanes, and capecitabine. The primary endpoint of the trial is overall survival (OS). Secondary endpoints include objective response rate (ORR), progression-free survival (PFS), and time to CNS disease progression or recurrence in patients with or without CNS lesions present at study entry.
Clinical Significance
The trial is motivated by findings from subgroup analyses of the Phase III BEACON trial, which suggested improved survival outcomes with etirinotecan pegol in certain patient populations. By focusing on patients with brain metastases, the ATTAIN trial aims to provide evidence for a targeted treatment approach in this difficult-to-treat population. The results of this trial could potentially offer a new therapeutic option for patients with advanced breast cancer and brain metastases, addressing an area of significant unmet medical need.
