Researchers at the University of Texas MD Anderson Cancer Center showed that adding metastasis-targeted radiation therapy to intermittent hormone therapy improved progression-free survival (PFS) in patients with oligometastatic prostate cancer. Results from the multicenter EXTEND trial were presented today at the 2022 American Society of Radiation Oncology (ASTRO) Annual Meeting.
At a median follow-up of 22.1 months, median PFS had not yet been reached in men who received the combination therapy, suggesting a significant improvement over the median PFS of 15.8 months in men who received only hormone therapy. The combination was well tolerated and extended the period that men could maintain a break from hormone therapy without progression, suggesting that this approach could improve the quality of life of men with advanced prostate cancer.
We know that radiation technology has evolved to directly target metastases, reduce side effects, and better treat men with prostate cancer. This study provides much-needed data on the benefits of combining these newer radiation techniques with hormone therapy to improve outcomes.”
Chad Tang, MD, principal investigator, associate professor of radiation oncology
Metastasis-targeted therapy (MDT) involves the direct local treatment of metastatic lesions using surgery or radiation, with the goal of killing all cancer cells in that location. Metastatic prostate cancer is generally treated with systemic therapies, the most common of which is continuous hormone therapy. The use of MDT to treat patients with oligometastatic disease has increased in recent years.
Oligometastatic cancer, which is defined as five or fewer metastases seen on imaging, represents a transitional state between localized and widespread metastatic disease. The first study showing benefit with definitive local therapy was conducted at MD Anderson and published in 2016. Since then, there has been substantial research in this area.
However, despite data supporting the benefits of initial hormone therapy and its synergy with radiation treatment, there have been no randomized trials testing this combination in patients with oligometastatic prostate cancer.
EXTEND is a Phase II randomized basket trial for multiple solid tumors testing whether the addition of MDT improves PFS for patients with oligometastatic cancer. PFS was prespecified and independently assessed and reported in 41 progression events, which occurred after a median follow-up of 22.1 months.
The prostate cancer cohort randomized 87 men to receive radiation plus intermittent hormone therapy or hormone therapy alone. The majority of participants (72 patients) were white, with seven black patients, six Hispanic patients, and two other patients included.
Hormonal therapy consisted of a luteinizing hormone-releasing hormone agonist/antagonist with or without a second-generation androgen receptor targeting agent. The benefits of MDT were preserved among patients regardless of whether they received a next-generation androgen-blocking agent. A planned break in hormone therapy occurred six months after enrollment, and all men resumed hormone therapy at progression.
As a secondary endpoint, the researchers also monitored how long the men were able to maintain normal testosterone levels while taking a break from hormone therapy. The addition of MDT prolonged the progression time; the median was not reached in the combination group, while the median time to progression was 6.1 months in men who received hormone therapy alone. These findings indicate that a strategy of radiation therapy and intermittent hormone therapy can maximize the time a man can safely maintain normal testosterone levels, which can preserve the patient’s quality of life.
Treatment was well tolerated, with three grade 3 toxicities observed in each arm. These consisted of impaired muscle movement as well as urinary and gastrointestinal side effects, but all were easily managed.
“This study shows that the combination of metastasis-targeted radiation and intermittent hormone therapy significantly improved progression-free survival, with manageable toxicities, for patients with oligometastatic disease,” Tang said. “I am encouraged that these data, combined with the knowledge gained in future trials, will allow us to safely preserve a man’s quality of life after this diagnosis.”
The researchers also performed exploratory analyzes of clinical samples, including flow cytometry and T-cell receptor sequencing, from peripheral blood at baseline and three-month follow-up. Their data demonstrated increases in markers of T-cell activation, proliferation and clonal expansion specifically in the combination therapy arm.
Additional research is needed to better understand these findings and identify biomarkers to predict which men will benefit from this treatment combination. A large randomized trial is needed to directly compare continuous hormone therapy with scheduled treatment breaks.
Source:
University of Texas MD Anderson Cancer Center