Addition of Metastasis-Directed Therapy to Standard of Care for Oligometastatic Disease: Primary Aggregated Analysis of All Baskets from the Phase II Randomized EXTEND Trial.

In 30 seconds

The multicenter, randomized phase II EXTEND trial evaluated whether adding metastasis-directed therapy (MDT) to standard-of-care (SOC) systemic therapy improves outcomes in patients with 1–5 metastases across six disease baskets. Among 334 patients analyzed per protocol, median follow-up was 53 months. Progression-free survival was longer with MDT + SOC than with SOC alone (hazard ratio, 0.54 [95% CI, 0.41 to 0.72], P < .001). Basket-specific results favored MDT in pancreas, prostate, and other cancers, while findings in breast and kidney cancers were inconclusive.

Key findings

• Across all baskets, MDT + SOC improved progression-free survival versus SOC alone (HR, 0.54 [95% CI, 0.41 to 0.72], P < .001).
• Excluding the prostate baskets, progression-free survival also favored MDT + SOC (HR, 0.60 [95% CI, 0.40 to 0.89]).
• Basket-specific progression-free survival superiority was identified for pancreas, prostate, and other cancers; breast and kidney results were inconclusive.
• Detectable ctDNA at enrollment correlated with shorter PFS and survival, while ctDNA clearance 3 months postenrollment correlated with improved survival.

Why it matters

The trial provides randomized evidence that adding metastasis-directed therapy may improve progression-free survival across a heterogeneous oligometastatic population. The differing basket-level signals caution against assuming equal benefit across tumour types and support further histology-specific testing. Associations involving ctDNA and immune activation also offer potential avenues for refining patient selection and understanding treatment effects.

What to keep in mind

This was a phase II trial with basket-specific analyses; results for breast and kidney baskets were inconclusive, and histology-specific efficacy signals require phase III testing.