In a clinical trial update, data from the STOMP and ORIOLE trials demonstrated that metastasis-directed therapy (MDT) remained associated with improved progression-free survival (PFS).
“The use of MDT is rapidly increasing in the setting of oligometastasis,” study researchers wrote. “STOMP and ORIOLE, the only two prospective trials of stereotactic ablative radiation versus observation in metachronous oligometastatic castration-sensitive prostate cancer (omCSPC), demonstrated that MDT, as compared with observation, prolong androgen deprivation–free survival and PFS.”
Long-term outcomes of these two trials were recently reported in The Journal of Clinical Oncology.
Both trials were phase-2 trials that included men with omCSPC who were randomly assigned to observation or MDT. Next-generation sequencing was used to test for high-risk mutations, defined as pathogenic somatic mutations within ATM, BRCA1/2, Rb1, or TP53.
Median follow-up for the group was 52.5 months. Median PFS was significantly prolonged with MDT compared with observation (pooled hazard ratio [HR]=0.44; 95% CI, 0.29-0.66; P<.001). The largest benefit in PFS was seen among men with high-risk mutations (HR=0.05 for high risk and HR=0.42 for not high-risk).
“Of note, the PFS beyond four years was 15%-20% with MDT regardless of mutation status, and thus, a sizable proportion of patients will experience durable response to therapy,” the researchers noted.
Among tumors with high-risk mutations the median PFS was 7.5 months for those treated with MDT compared with 2.8 months for those assigned observation (P<.01). Among patients assigned to MDT, the PFS was 13.4 months in those without a high-risk mutation compared with 7.5 month for those with a high-risk mutation (P=.09).
“This suggests that individuals with omCSPC without a high-risk mutation might initially be treated with MDT alone and conversely highlights the need for novel treatment paradigms in those with a high-risk mutation,” the researchers wrote.
They went on to emphasize that both those with and without high-risk mutations appeared to benefit from MDT. This suggests “that this therapy should be offered to most, if not all, omCSPC.”