Dr Ludmir on the Rationale For the EXTEND Trial in PDAC

Ethan B. Ludmir, MD, assistant professor, Department of Gastrointestinal Radiation Oncology, research consultant, Division of Radiation Oncology, assistant professor, Department of Biostatistics, The University of Texas MD Anderson Cancer Center; clinical assistant professor, Department of Biomedical Sciences, The University of Houston College of Medicine, discusses the rationale for and the outcomes derived from the phase 2 EXTEND trial (NCT03599765) in patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC).

This multi-center randomized phase 2 basket trial investigated the addition of metastasis-directed local therapy to standard-of-care systemic therapy in patients with oligometastatic pancreatic cancer Ludmir begins. Prior research showing that patients with limited metastatic sites have benefited from a combination of local and systemic therapy supported the study’s inception.

Between 2019 and 2023, 41 patients were enrolled onto the study, 40 of whom were efficacy evaluable. Patients with 5 or fewer metastatic sites suitable for metastasis-directed therapy were randomly assigned to receive standard systemic therapy or metastasis-directed therapy with systemic therapy continuation. Key stratification factors included the number of metastatic lesions, prior systemic therapy lines, and CA-19-9 levels. The primary end point was progression-free survival (PFS).

esults demonstrated a notable improvement in median PFS with metastasis-directed local therapy plus systemic therapy, Ludmir states.

Patients in the control arm achieved a median PFS of 2.5 months, whereas those receiving metastasis-directed therapy experienced a median PFS of 10.3 months, he continues. This corresponded with a hazard ratio of 0.43 and a P value of 0.03, indicating a statistically significant enhancement in PFS, Ludmir concludes.

These findings indicate the efficacy and safety of metastasis-directed therapy for patients with oligometastatic PDAC. However, larger trials are needed to validate the survival benefit seen with metastasis-directed local therapy and explore systemic immune activation as a potential mechanism for therapy benefit.