Adding Metastasis-Directed Therapy to Standard-of-Care Systemic Therapy for Oligometastatic Breast Cancer (EXTEND): A Multicenter, Randomized Phase 2 Trial.

Purpose: Prior evidence suggests a progression-free survival (PFS) benefit from adding metastasis-directed therapy (MDT) to standard-of-care (SOC) systemic therapy for patients with some oligometastatic solid tumors. Randomized trials testing this hypothesis in breast cancer have yet to be published. We sought to determine whether adding MDT to SOC systemic therapy improves PFS in oligometastatic breast cancer.

Methods And Materials: External Beam Radiation to Eliminate Nominal Metastatic Disease is a multicenter phase 2 randomized basket trial testing the addition of MDT to SOC systemic therapy in patients with ≤5 metastases (NCT03599765). Patients were randomly assigned 1:1 to MDT (definitive local treatment to all sites of disease, plus SOC systemic therapy) or to SOC systemic therapy-only. Primary endpoint was PFS, and secondary endpoints included overall survival, time to subsequent line of systemic therapy, and time to the appearance of new metastases. Exploratory analyses included quality of life and systemic immune response measures.

Results: From September 2018 through July 2022, 22 and 21 patients were randomly assigned to the MDT and no-MDT arms, respectively. At a median follow-up of 24.8 months, PFS was not improved with the addition of MDT to SOC systemic therapy (median PFS 15.6 months MDT vs 24.9 months no-MDT [hazard ratio, 0.91; 95% CI, 0.34-2.48; P = .86]). Similarly, MDT did not improve overall survival, time to subsequent line of systemic therapy, or time to the appearance of new metastases (all P > .05). No significant differences were found in quality of life measures, systemic T-cell activation, or T-cell stimulatory cytokine concentration.

Conclusions: Among patients with oligometastatic breast cancer, the addition of MDT to SOC systemic therapy did not improve PFS. These findings suggest that MDT may have no systemic benefit in otherwise unselected patients with oligometastatic breast cancer, although this trial was limited by a heterogeneous and small sample size and overperformance of both treatment arms.