More from ASTRO 2019 [1]:
“The aim of the ORIOLE trial was to treat prostate cancer that has spread to a limited number of sites beyond the prostate with precisely targeted radiation in hopes of preventing or delaying further progression of disease while delaying initiation of hormone therapy which, while effective, has its own potential for side effects and eventual development of resistance.”
"The trial involved 54 patients with recurrent, hormone sensitive oligometastatic prostate cancer whose cancer had spread to a limited number of sites outside the prostate after treatment with surgery or radiation. They were randomized to observation with no further treatment for 6 months (n = 19) or to receive stereotactic ablative radiotherapy (SABR, n = 35), a high-precision therapy in which high doses of radiation are targeted to the tumor in one or several sessions.
"SABR outperformed observation, with increased levels of prostate specific antigen (PSA) being less likely. The patients also lived significantly longer without any detectable disease progression; with disease progression noted in 19% of patients treated with SABR, compared with 61% of those in the observation arm in an intent-to-treat analysis ... The median progression-free survival (PFS) time was 5.8 months in the observation arm and not reached in the SABR arm ..."
-Patrick
[1] practiceupdate.com/content/...
September 15, 2019—Chicago, Illinois—The therapeutic value of radiation that is precisely delivered as a high dose in the treatment of men with oligometastatic prostate cancer has been demonstrated in randomized, phase II trial presented here at the 2019 Annual Meeting of the American Society for Radiation Oncology, taking place from September 15 to 19.
While the ORIOLE trial was small, with only 54 patients, the results point the way for the therapy to be used as an effective and safe option for patients who wish to delay hormone-suppression therapy.
“Our primary clinical findings were that targeted radiation safely decreased the risk of disease progression in our patients while sparing them the side effects associated with hormone therapy,” presenter Ryan Phillips, MD, PhD, of the Johns Hopkins School of Medicine in Baltimore, told Elsevier’s PracticeUpdate. The finding that the therapy stimulated an immune response was an unexpected bonus, since this has been considered impossible in this type of cancer.
“While advances in medical management over the past few years have improved our ability to control metastatic prostate cancer, it is still ultimately an incurable, life-limiting disease, and new approaches need to be explored in order to improve the length and quality of our patients lives,” said Dr. Philips. “The aim of the ORIOLE trial was to treat prostate cancer that has spread to a limited number of sites beyond the prostate with precisely targeted radiation in hopes of preventing or delaying further progression of disease while delaying initiation of hormone therapy which, while effective, has its own potential for side effects and eventual development of resistance.”
The trial involved 54 patients with recurrent, hormone sensitive oligometastatic prostate cancer whose cancer had spread to a limited number of sites outside the prostate after treatment with surgery or radiation. They were randomized to observation with no further treatment for 6 months (n = 19) or to receive stereotactic ablative radiotherapy (SABR, n = 35), a high-precision therapy in which high doses of radiation are targeted to the tumor in one or several sessions.
SABR outperformed observation, with increased levels of prostate specific antigen (PSA) being less likely. The patients also lived significantly longer without any detectable disease progression; with disease progression noted in 19% of patients treated with SABR, compared with 61% of those in the observation arm in an intent-to-treat analysis (P = .005). The median progression-free survival (PFS) time was 5.8 months in the observation arm and not reached in the SABR arm (hazard ratio 0.30, P = .002).
Among the 35 patients in the SABR arm who received prostate-specific membrane antigen-positron emission tomography or computed tomography (PSMA PET or CT) at baseline and 6 months, those with total consolidation of radiotracer-avid disease were less likely to develop new lesions at 6 months (16% vs 63%, P = 0.006) and had significantly longer median PFS (unreached vs 11.8 months, P = .003) as well as distant metastasis-free survival (29 vs 6.0 months, P = .0008).
“Any treatment has the potential for side effects and must be considered carefully, but we did not identify any serious toxicities associated with our radiation,” said Dr. Phillips.
Examinations done prior to and 90 days following radiation exposure revealed significant and measurable changes, similar to those that occur in vaccination, in T cells. These changes did not occur in patients in the observation arm. In a press conference, Dr. Phillips opined that radiation may provide a stimulus to the immune system to more aggressively fight the cancer.
The finding is the first indication that SABR can induce a systemic immune response in patients with prostate cancer. “Exciting findings from our correlative studies, while preliminary and requiring additional investigation, suggest that advanced imaging with PSMA PET may provide valuable information to help improve the effectiveness of our treatments, that radiation induces an immune response similar in magnitude to a vaccination, and that it may be possible to select which patients are most likely to benefit from our approach using a sophisticated blood test called circulating tumor DNA analysis,” Dr. Phillips told PracticeUpdate.
“One limitation of ORIOLE is that most of our patients who were initially observed were eventually treated with the same targeted radiation that our treatment group received upfront, which limits our ability to determine the long-term differences between the arms of our trial,” he continued. “Additionally, the excellent medical treatments available for men with metastatic prostate cancer have improved the average life expectancy associated with this diagnosis such that it will likely be many years before we would be able to determine if the average total life expectancy of our patients has been improved using this treatment approach. Finally, the correlative studies we performed provide interesting hypotheses for future investigations but are limited by the relatively small number of patients we treated.”
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