Radiation plus intensive systemic therapy improves outcomes in prostate cancer subset
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Key takeaways:
- Adding radiation therapy to standard care significantly extended radiographic PFS but not OS.
- Radiation therapy significantly delayed the onset and frequency of serious disease-related genitourinary events.
CHICAGO Adding prostate irradiation to standard systemic therapy extended radiographic PFS among men with newly diagnosed low-volume metastatic castration-sensitive prostate cancer, according to results of the PEACE-1 trial.
Although the regimen did not confer an OS benefit, the addition of radiation therapy to an intensified standard-of-care regimen produced the best efficacy and safety outcomes, findings from the randomized phase 3 study presented at ASCO Annual Meeting showed.
Data derived from Bossi A, et al. Abstract LBA5000. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago.
“Combining prostate radiation therapy with intensified systemic treatment improves radiographic PFS and castration-resistant prostate cancer-free survival [for] men with low-burden, de novo metastatic castration-resistant prostate cancer,” Alberto Bossi, MD, of Amethyst RT Group in France, said during a presentation “A triplet of [androgen deprivation therapy] plus abiraterone plus prostate radiation therapy should be considered as a new standard therapy option [for] these men.”
Background and methods
The treatment landscape for men with newly diagnosed metastatic castration-sensitive prostate cancer has evolved rapidly over the last decade, Bossi said.
The accrual of patients to the PEACE-1 trial coincided with this evolution, starting with androgen deprivation therapy alone as the standard in 2013 and continuing to the current era of systemic triplet therapy that includes ADT, docetaxel and abiraterone acetate (Zytiga, Janssen).
During ASCO Annual Meeting, Bossi presented the results of a second preplanned primary endpoint analysis to assess the effect of prostate irradiation on safety and outcomes among men with low-volume disease receiving intensified systemic therapy.
The multicenter PEACE-1 trial included 1,172 men with newly diagnosed metastatic castration-sensitive prostate cancer.
The 2×2 factorial design study randomly assigned participants in a 1:1:1:1 ratio to standard of care (ADT plus docetaxel), standard of care plus abiraterone, standard of care plus radiotherapy of the primary tumor, or standard of care plus abiraterone and radiotherapy of the primary tumor.
Researchers enrolled patients from November 2013 through December 2018.
ADT alone or ADT plus docetaxel at the investigator’s discretion served as the standard of care until 2017, when researchers restricted study accrual to men receiving ADT plus docetaxel.
Overall, 584 men (median age, 66 years; range, 37-94) received standard of care plus radiotherapy, and 588 men (median age, 67 years; range, 43-88) received standard therapy alone. A comparable number of men in each treatment group had low-volume disease (radiotherapy, n = 252; standard therapy alone, n = 253).
Radiographic PFS and OS served as dual primary endpoints. Secondary endpoints included castration resistance-free survival, serious genitourinary EFS and treatment-related toxicity.
Key findings
Median follow-up was 6.1 years (73 months).
Researchers observed a “qualitative interaction between radiation therapy and abiraterone” for radiographic PFS among men with low-volume disease (P = .026).
Separate assessments of each experimental arm revealed the addition of radiotherapy alone to standard care did not significantly increase median radiographic PFS (3 years for standard care vs. 2.6 years for standard care plus radiotherapy; HR=1.11; 99.9% CI, 0.67-1.84).
However, median radiographic PFS improved to 4.4 years with standard care plus abiraterone (HR = 0.76; 99.9% CI, 0.45-1.28) and to 7.5 years with standard care plus abiraterone and radiotherapy (HR = 0.5; 99.9% CI, 0.28-0.88) compared with standard care alone.
Investigators reported an HR of 0.65 (99.9% CI, 0.36-1.19) between the two abiraterone treatment arms.
The study did not meet its predefined threshold for a statically significant interaction for OS.
Researchers reported median OS of 6.9 years among men who received standard of care plus abiraterone compared with 7.5 months among those who received standard care plus abiraterone and radiation therapy (HR = 0.98; 95% CI, 0.74-1.28).
Compared with those who received standard care plus abiraterone only, the addition of radiation therapy had a significant impact on delaying time from randomization to occurrence of serious genitourinary events (P = .0006). Even radiotherapy alone added to standard care conferred a statistically significant benefit in delaying serous genitourinary events (P = .003).
The addition of radiotherapy to intensive standard therapy did not result in overall increased toxicity, Bossi said.
Investigators reported hypertension as the most frequent grade 3 to grade 5 treatment-related toxicity, occurring among 18% of men who received standard therapy plus abiraterone compared with 23% among those who received additional radiation therapy.
Clinical implications
The results show “clear statistical evidence that the addition of abiraterone plus radiotherapy confers a survival advantage” compared with standard therapy only, Bossi said.
“There appears to be a clear synergistic effect between abiraterone and radiotherapy,” he said. “For the first time, PEACE-1 also establishes a role for radiation therapy in the prevention of serious genitourinary events, irrespective of the patients’ metastatic burden.”
Perspective
Back to TopBiren Saraiya, MD
The PEACE-1 trial studied two interventions among men with de novo metastatic prostate cancer: abiraterone and prostate radiation.
Over the past decade, treatment for de novo metastatic prostate cancer has moved toward a “more is better” approach, with evidence showing doublets of ADT chemotherapy (docetaxel) or novel hormone therapies (abiraterone, enzalutamide [Xtandi; Astellas, Pfizer], apalutamide [Erleada, Janssen] and darolutamide [Nubeqa, Bayer]) with chemotherapy conferring better outcomes than ADT alone. Further studies suggested a triplet of abiraterone and olaparib (Lynparza; AstraZeneca, Merck) perform better than doublets for patients with BRCA alterations.
The PEACE-1 trial adds potential radiation to the prostate in addition to abiraterone, ADT and possibly docetaxel.
In terms of incorporating prostate radiation into treatment for low-volume de novo metastatic prostate cancer, we must be careful when interpreting the data in current practice conditions with routine use of much more sensitive imaging tests, such as PSMA PET. Men with PSMA PET-defined low-volume disease — for example, a small lymph node in the pelvis or a small bone metastasis — without clearly defined metastatic disease on conventional imaging were not part of this patient population. This study surprisingly did not report an OS benefit. A detailed peer-reviewed publication is needed to understand why and would be important before we incorporate this approach into routine care for our patients.
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Bossi A, et al. Abstract LBA5000. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago.
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