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

Researchers at The University of Texas MD Anderson Cancer Center demonstrate that adding radiotherapy for metastases to intermittent hormone therapy improves progression-free survival (PFS) in patients with oligometastatic prostate cancer Did. Results from the multicenter EXTEND trial were presented today at the 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting.

With a median follow-up of 22.1 months, median PFS for men receiving combination therapy was not yet achieved, suggesting significant improvement over median PFS of 15.8 months for men receiving hormone therapy alone doing. This combination therapy was well tolerated and increased the length of time men were able to remain off hormone therapy without progression, suggesting this approach may improve quality of life for men with advanced prostate cancer It was suggested that there is

We know that radiation techniques have evolved to directly target metastases, reduce side effects, and better treat men with prostate cancer. It provides much-needed data on the benefits of combining hormonal therapy with new radiological techniques in

Chad Tan, MD, PChief Investigator, AAssociate Professor of Radiation Oncology

Metastasis-directed therapy (MDT) involves direct local treatment of metastatic lesions with surgery or radiation, with the goal of killing all cancer cells there. Metastatic prostate cancer is commonly treated with systemic therapy, 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, defined as having 5 or fewer imaging metastases, represents a transitional state between localized and extensive metastatic disease. The first study showing definitive local therapy benefits was conducted at MD Anderson and published in 2016. Since then, considerable research has been done in this area.

However, despite data supporting the benefits of upfront hormonal therapy and its synergistic effect with radiotherapy, there are no randomized trials testing this combination in patients with oligometastatic prostate cancer.

The EXTEND trial is a Phase II randomized basket study in multiple solid tumors to test whether the addition of MDT improves PFS in patients with oligometastatic disease. PFS was prespecified to be independently assessed and reported in 41 progression events occurring after a median follow-up of 22.1 months.

In the prostate cancer cohort, 87 men were randomized to receive radiation therapy plus intermittent hormone therapy or hormone therapy alone. Most participants (72 patients) were Caucasian, including 7 black patients, 6 Hispanic patients, and 2 other patients.

Hormone therapy consisted of a luteinizing hormone-releasing hormone agonist/antagonist with or without a second-generation androgen receptor-targeting agent. The benefit of MDT was maintained across patients regardless of whether they received new-generation androgen blockers. A scheduled hormonal therapy discontinuation was performed 6 months after enrollment, and all men resumed hormonal therapy upon progression.

As a secondary endpoint, the researchers also monitored how long men were able to maintain normal testosterone levels during a break from hormone therapy.Adding MDT increased time to progression. The median time to progression was not reached in the combination group, but in the man who received hormone therapy alone, he had a median time to progression of 6.1 months. These findings demonstrate that a strategy of radiotherapy and intermittent hormone therapy can maximize the time men can safely maintain normal testosterone levels and preserve the patient’s quality of life.

The 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, all of which were easily managed.

“This study shows that the combination of metastatic radiation therapy and intermittent hormone therapy significantly improved progression-free survival with manageable toxicity in patients with oligometastatic disease,” said Tang. said. “By combining this data with the knowledge gained in future trials, we are confident that we will be able to safely maintain the quality of life for men following this diagnosis.”

Researchers also used flow cytometry and T cells Receptor sequencing from peripheral blood at baseline and 3-month follow-up. Their data show that markers of T cell activation, proliferation, and clonal expansion are increased, especially in the combination therapy group.

Additional research is needed to better understand these findings and to identify biomarkers that predict which men will benefit from this treatment combination. Large randomized trials are needed to directly compare discontinuation.