https://ascopubs.org/doi/pdf/10.1200/JCO.24.00081 ## Literature Card: EXTEND — MDT for Oligometastatic PDAC **Citation** Ludmir EB, Sherry AD, Fellman BM, et al. **Addition of Metastasis-Directed Therapy to Systemic Therapy for Oligometastatic Pancreatic Ductal Adenocarcinoma (EXTEND): A Multicenter, Randomized Phase II Trial.** _J Clin Oncol._ 2024. DOI: 10.1200/JCO.24.00081. ### Clinical Question In patients with **oligometastatic PDAC**, does adding **comprehensive metastasis-directed therapy (MDT)** to systemic therapy improve outcomes compared with systemic therapy alone? ### Study Design - **Multicenter randomized phase II basket trial** - PDAC cohort within **EXTEND** - **N = 41 randomized**, **40 eligible for primary PFS analysis** - Randomized **1:1** - Systemic therapy alone - Systemic therapy + MDT to all known metastatic sites - Eligibility: **≤5 metastatic sites** - Primary endpoint: **PFS** - Progression defined by **RECIST 1.1, clinical progression, or death** ### Intervention **MDT + systemic therapy**, usually using ablative local therapy/radiation to all known metastatic lesions. ### Key Results |Outcome|MDT + systemic therapy|Systemic therapy alone| |---|---|---| |Median PFS|**10.3 mo**|**2.5 mo**| |HR for PFS|**0.43**|—| |P value|**0.030**|—| |Grade ≥3 MDT-related toxicity|**0 reported**|—| Median follow-up was **17 months**. PFS improved significantly with MDT. No grade ≥3 adverse events attributed to MDT were observed. ### Main Takeaway Adding MDT to systemic therapy in carefully selected **oligometastatic PDAC** patients produced a large **PFS benefit** with minimal apparent added toxicity. ### Why It Matters This supports the concept that a subset of metastatic PDAC may behave as **oligometastatic disease**, where aggressive treatment of all visible disease can delay progression and delay systemic therapy escalation. ### Major Caveat This is **not practice-defining yet**. It is small, phase II, highly selected, and the clinically decisive endpoint is **OS**, not PFS. ### My Interpretation Useful tumor board framing: > In selected oligometastatic PDAC patients with limited metastatic burden, good performance status, controlled disease on chemotherapy, favorable CA19-9 trajectory, and safely targetable lesions, MDT can be considered, preferably on trial or with careful multidisciplinary selection. ### Board / Practice Pearl Do **not** generalize this to all metastatic PDAC. Think of MDT as a strategy for **selected oligometastatic biology**, not as routine consolidation for broadly metastatic disease. ### Limitations - Small PDAC cohort - Phase II design - PFS primary endpoint - Highly selected population - OS benefit not established - Possible guarantee-time/selection bias from patients who remain well enough for MDT - Heterogeneity in systemic therapy and disease biology ### Future Direction The phase III **EXPAND** trial is designed to test whether MDT improves **PFS and OS** in oligometastatic pancreatic cancer.