Synthetic Evidence Corpus

Corpus record OMC_0007

Long-term progression-free survival and genomic predictors after metastasis-directed therapy versus observation for oligometastatic castration-sensitive prostate cancer: pooled STOMP and ORIOLE trial analysis

Deek MP, Van der Eecken K, Sutera P, Deek RA, Fonteyne V, Mendes AA, Decaestecker K, Kiess AP, Lumen N, Phillips R, De Bruycker A, Mishra M, Rana Z, Molitoris J, Lambert B, Delrue L, Wang H, Lowe K, Verbeke S, Van Dorpe J, Bultijnck R, Villeirs G, De Man K, Ameye F, Song DY, DeWeese T, Paller CJ, Feng FY, Wyatt A, Pienta KJ, Diehn M, Bentzen SM, Joniau S, Vanhaverbeke F, De Meerleer G, Antonarakis ES, Lotan TL, Berlin A, Siva S, Ost P, Tran PT

Journal
Journal of Clinical Oncology
Year
2022
Study type
pooled analysis of randomized phase II trials
Disease area
oligometastatic castration-sensitive prostate cancer

Abstract

Clinical trials often evaluate multiple end points that mature at different times; initial reports, typically based on the primary end point, may be published before planned co-primary or secondary analyses are available. This Clinical Trial Update reports additional results after prior publication of the primary end point. The initial STOMP and ORIOLE trial reports suggested that metastasis-directed therapy (MDT) for oligometastatic castration-sensitive prostate cancer (omCSPC) was associated with improved treatment outcomes. We pooled STOMP and ORIOLE to assess long-term outcomes of MDT versus observation in omCSPC and to evaluate whether a high-risk somatic mutational signature could risk stratify outcomes after MDT. The primary end point was progression-free survival (PFS), calculated using the Kaplan-Meier method. High-risk mutations were defined as pathogenic somatic mutations in ATM, BRCA1/2, Rb1, or TP53. Median follow-up for the whole group was 52.5 months. Median PFS was prolonged with MDT compared with observation (pooled hazard ratio [HR], 0.44; 95% CI, 0.29 to 0.66; P < .001), with the largest MDT benefit in patients with a high-risk mutation (HR high-risk, 0.05; HR no high-risk, 0.42; P for interaction = .12). Within the MDT cohort, PFS was 13.4 months in patients without a high-risk mutation and 7.5 months in patients with a high-risk mutation (HR, 0.53; 95% CI, 0.25 to 1.11; P = .09). Long-term outcomes from the only two randomized trials in omCSPC suggest sustained clinical benefit for MDT over observation. A high-risk mutational signature may help risk stratify outcomes after MDT.