Metastasis-Directed Therapy Plus Intermittent Hormone Therapy Improves PFS in Oligometastatic Prostate Cancer

Metastasis-directed therapy (MDT) seemed to prolong progression-free survival (PFS) in combination with intermittent hormone therapy vs hormone therapy alone and even increased time off of hormone therapy in the treatment of oligometastatic prostate cancer, according to early data from the phase 2 EXTEND trial (NCT03599765) presented at the 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting.

At a median follow-up of 22.1 months, median PFS in the MDT plus hormone therapy arm was not reached (NR) vs 15.8 months in the hormone therapy alone arm (HR 0.25; 95% CI, 0.12-0.55; P <.001). The MDT arm vs the hormone therapy arm also experienced improved time from eugonad testosterone level to progression (median, NR vs 6.1 months, P = .023). The rate of new lesions at 2 years was 33% in the MDT group vs 42% in the hormone therapy group (P = .04). The treatments had similar safety profiles, with 3 grade 3 toxicities in both arms. Additionally, flow cytometry and TCR sequencing uncovered increases in markers of T cell activation, proliferation, and clonal expansion in the MDT arm.

“EXTEND represents the first randomized study to evaluate MDT with hormone therapy in oligometastatic prostate cancer and demonstrated improvement in PFS and eugonad PFS. Combination of MDT with intermittent hormone therapy may allow for…excellent disease control while facilitating prolonged eugonad testosterone intervals,” investigators wrote.

This multicenter randomized basket trial enrolled 87 patients with histologically confirmed oligometastatic prostate cancer with no more than 5 metastatic lesions and at least 2 prior months of hormone therapy at the time of study entry. Participants were randomly assigned to continue hormone therapy with or without MDT after at least 2 months of hormone therapy alone. As planned, patients halted hormone therapy 6 months after enrollment and did not resume until progression. Hormone therapy included a luteinizing hormone-releasing agonist or antagonist plus or minus a second-generation androgen receptor targeting agent. The study’s primary end point was PFS.

The trial selected for patients with no more than 4 prior lines of systemic therapy targeted against metastatic disease who had an ECOG performance status of 0 to 2. Other inclusion criteria included an absolute neutrophil count of at least 500/mcL, a platelet count of at least 25,000/mcL, and a hemoglobin count of at least 7 g/dL. Patients were excluded if they had active scleroderma, lupus, or rheumatologic disease which would preclude safe radiation therapy, metastatic effusion, or diffuse metastatic processes such as leptomeningeal disease, diffuse bone marrow involvement, or peritoneal carcinomatous.

Findings from a subgroup analysis also identified PFS improvement among those treated with MDT who received a SART (HR 0.24; 95% CI, 0.08-0.71) vs those who didn’t (HR 0.36; 95% CI, 0.15-0.83).

Reference

Tang C, Sherry AD, Haymaker C, et al. Addition of metastasis-directed therapy to intermittent hormone therapy for oligometastatic prostate cancer (EXTEND): a multicenter, randomized phase II trial. Presented at 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting; October 23-26, 2022; San Antonio, TX; abstract LBA05. Accessed October 28, 2022.