Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available.
Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The initial STOMP and ORIOLE trial reports suggested that metastasis-directed therapy (MDT) in oligometastatic castration-sensitive prostate cancer (omCSPC) was associated with improved treatment outcomes. Here, we present long-term outcomes of MDT in omCSPC by pooling STOMP and ORIOLE and assess the ability of a high-risk mutational signature to 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 within ATM, BRCA1/2, Rb1, or TP53. The 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 value < .001), with the largest benefit of MDT in patients with a high-risk mutation (HR high-risk: 0.05; HR no high-risk: 0.42; P value for interaction: .12). Within the MDT cohort, the PFS was 13.4 months in those without a high-risk mutation, compared with 7.5 months in those 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 a sustained clinical benefit to MDT over observation. A high-risk mutational signature may help risk stratify treatment outcomes after MDT.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2022 Aug 24 [Epub ahead of print]
Matthew P Deek, Kim Van der Eecken, Philip Sutera, Rebecca A Deek, Valérie Fonteyne, Adrianna A Mendes, Karel Decaestecker, Ana Ponce Kiess, Nicolaas Lumen, Ryan Phillips, Aurélie De Bruycker, Mark Mishra, Zaker Rana, Jason Molitoris, Bieke Lambert, Louke Delrue, Hailun Wang, Kathryn Lowe, Sofie Verbeke, Jo Van Dorpe, Renée Bultijnck, Geert Villeirs, Kathia De Man, Filip Ameye, Daniel Y Song, Theodore DeWeese, Channing J Paller, Felix Y Feng, Alexander Wyatt, Kenneth J Pienta, Maximillian Diehn, Soren M Bentzen, Steven Joniau, Friedl Vanhaverbeke, Gert De Meerleer, Emmanuel S Antonarakis, Tamara L Lotan, Alejandro Berlin, Shankar Siva, Piet Ost, Phuoc T Tran
Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ., Department of Pathology and Human Structure and Repair, University of Ghent, Ghent, Belgium., Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD., Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium., Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD., Department of Urology, Ghent University Hospital, Ghent, Belgium., Department of Radiation Oncology, Mayo Clinic, Rochester, MN., Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD., Department of Radiology and Nuclear Medicine, Ghent University, and Department of Nuclear Medicine, AZ Maria-Middelares Ghent, Belgium., Department of Radiology, Ghent University Hospital, Ghent, Belgium., Department of Pathology, Ghent University Hospital, Ghent, Belgium., Department of Nuclear Medicine, Ghent University Hospital, Ghent, Belgium., Department of Urology, AZ Maria-Middelares Ghent, Ghent, Belgium., Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD., Departments of Medicine, Urology and Radiation Oncology, UCSF, San Francisco, CA., Department of Urologic Sciences, University of British Columbia, and Vancouver Prostate Centre, Vancouver, Canada., Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA., Department of Urology, Catholic University Leuven, Leuven, Belgium., Department of Urology, AZ Nikolaas, Sint-Niklaas, Belgium., Department of Radiation Oncology, Catholic University Leuven, Leuven, Belgium., Department of Medicine, University of Minnesota School of Medicine, Minneapolis, MN., Department of Radiation Oncology, Princess Margaret Cancer Center, Toronto, Canada., Department of Radiation Oncology, Peter MacCallum Cancer Center, Melbourne Australia., Department of Radiation Oncology, Iridium Network, Antwerp, Belgium.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/36001857