Combination treatment improves progression-free survival in patients with oligometastatic prostate cancer

Combination treatment improves progression-free survival in patients with oligometastatic prostate cancer

Researchers at the University of Texas MD Anderson Cancer Center showed that adding metastatic-directed radiation therapy to intermittent hormone therapy improved progression-free survival (PFS) in patients with oligometastatic prostate cancer. Results from the multicenter EXTEND study were presented today at the 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting.

At a median follow-up of 22.1 months, the median PFS had not yet been reached in men receiving combination therapy, indicating a significant improvement over the median PFS of 15.8 months in men receiving hormone therapy alone. The combination was well tolerated and extended the amount of time men could stop hormone therapy without progression, suggesting this approach could improve the quality of life for men with advanced prostate cancer.

We know that radiation technology has evolved to directly attack 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, PPrincipal investigator, Aassociated professor of radiation oncology

Metastasis-directed therapy (MDT) involves direct local treatment of metastases through surgery or radiation with the aim of killing all cancer cells at that site. Metastatic prostate cancer is generally treated with systemic therapies, the most common of which is continuous hormonal therapy. The use of MDT to treat patients with oligometastatic disease has increased in recent years.

Oligometastatic cancer, defined as five or fewer metastases visible on imaging, represents a transitional state between localized and widespread metastatic disease. The first study showing the benefit of definitive local therapy was conducted at MD Anderson and published in 2016. Since then, intensive research has been carried out in this area.

However, despite the data supporting the benefits of upfront hormone therapy and its synergy with radiation treatment, there have been no randomized trials evaluating this combination in patients with oligometastatic prostate cancer.

EXTEND is a phase II, randomized, multi-solid tumor basket trial testing whether the addition of MDT improves PFS in patients with oligometastatic cancer. PFS was predetermined to be independently assessed and reported in 41 progression events that occurred after a median follow-up of 22.1 months.

The Prostate Cancer Cohort randomized 87 men to receive either radiation plus intermittent hormone therapy or hormone therapy alone. Most participants (72 patients) were white, including seven black patients, six Hispanic patients, and two other patients.

Hormone therapy consisted of a luteinizing hormone releasing agonist/antagonist, with or without a second generation androgen receptor targeting agent. The benefits of MDT were maintained in all patients, regardless of whether they received a newer generation androgen blocker. A planned interruption of hormone therapy occurred six months after enrollment, and all men resumed hormone therapy upon progression.

As a secondary endpoint, researchers also monitored the time men were able to maintain normal testosterone levels during their hormone therapy break. Addition of MDT increased time to progression; the median was not reached in the combination group, while the median time to progression in men receiving hormone therapy alone was 6.1 months. These results suggest that a strategy of radiation therapy and intermittent hormone therapy can maximize the time a man can safely maintain normal testosterone levels, thereby preserving 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 and urinary and gastrointestinal side effects, but all were easily managed.

"This study shows that the combination of metastatic-directed radiation and intermittent hormonal therapy significantly improves progression-free survival with manageable toxicities for patients with oligometastatic disease," said Tang. "I am encouraged that these data, combined with findings from future studies, will allow us to safely preserve a man's quality of life after this diagnosis."

The researchers also conducted exploratory analyzes on clinical samples, including flow cytometry and T-cell receptor sequencing, from peripheral blood at baseline and three months of follow-up. Their data showed an increase in markers of T cell activation, proliferation and clonal expansion, particularly in the combination therapy arm.

Further research is needed to better understand these results 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 planned treatment breaks.

Source:

University of Texas MD Anderson Cancer Center

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