2019 ASCO Annual Meeting!
Session: Melanoma/Skin Cancers
Type: Oral Abstract Session
Time: Tuesday June 4, 9:45 AM to 12:45 PM
Phase 3 international trial of adjuvant whole brain radiotherapy (WBRT) or observation (Obs) following local treatment of 1-3 melanoma brain metastases (MBMs).
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 9500)
Author(s): Gerald Fogarty, Kari Dolven-Jacobsen, Rachael L. Morton, George Hruby, Anna K. Nowak, Janette L. Vardy, Katharine J. Drummond, Haryana M. Dhillon, Catherine Mandel, Richard A. Scolyer, Brindha Shivalingham, Mark R. Middleton, Bryan H. Burmeister, Serigne Lo, Claudius H. Reisse, Elizabeth J. Paton, Victoria Steel, Narelle C. Williams, John F. Thompson, Angela M. Hong; Melanoma Institute Australia, The University of Sydney, Mater Hospital, Genesis Care, Australia and New Zealand Melanoma Trials Group, University of Notre Dame, University of Technology, Sydney, NSW, Australia; Oslo University Hospital, The Radium Hospital, Oslo, Norway; Melanoma Institute Australia, NHMRC Clinical Trials Centre, The University of Sydney, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Royal North Shore Hospital, Sydney, NSW, Australia; Medical School, University of Western Australia, Perth, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Department of Neurosurgery, Royal Melbourne Hospital, Department of Surgery, University of Melbourne, Parkville, VIC, Australia; University of Sydney, Sydney Medical School, Sydney, NSW, Australia; Swinburne University of Technology, Melbourne, VIC, Australia; Melanoma Institute Australia, The University of Sydney, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Royal Prince Alfred Hospital, Sydney, NSW, Australia; University of Oxford, Oxford, United Kingdom; Genesis Care, Fraser Coast, Hervey Bay, QLD, Australia; Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia; Oslo University Hospital, Oslo, Norway; Australia and New Zealand Melanoma Trials Group, The University of Sydney, Sydney, NSW, Australia; Melanoma Institute Australia, Department of Melanoma and Surgical Oncology at Royal Prince Alfred Hospital, Sydney, NSW, Australia; Melanoma Institute Australia, The University of Sydney, Mater Hospital, Genesis Care, Sydney, NSW, Australia
Background: The role of adjuvant WBRT in MBMs is controversial. This trial compares WBRT with Obs after local treatment of 1-3 MBMs. Methods: The primary endpoint is distant intracranial failure (DIF) within 12 months of randomization. The a priori neurocognitive function (NCF) endpoint is Hopkins Verbal Learning Test-Revised (HVLT-R) delayed recall at 4 months. Secondary endpoints include local failure (LF), overall survival (OS) and global quality of life (QoL). Analyses were conducted on intention-to-treat basis with nominal two-sided significance level 5%. Drug therapy was allowed. Effective drugs became available during trial and their impact was analysed. Results: Of 586 eligible patients (pts), 215 consented from 31 sites in 3 countries (Australia, UK and Norway) between 2009 and 2017. Eight (0.04%) who withdrew or had no data collected were excluded. 107 randomized to Obs and 100 to WBRT. Mean age 62 years, 67% males, 61% with single MBM of mean size 2cm, 67% had extracranial disease at randomization. The two arms were well matched. NCF was completed by English speakers; 50 WBRT and 70 Obs at baseline, declining to 26 and 35 respectively at 4 months. Within 12 months, 54 (50.5%) Obs had DIF compared with 42 (42.0%) WBRT pts (OR 0.71; 95%CI 0.41-1.23; p = 0.222). There was no difference in LF (p = 0.100) or OS (log-rank p = 0.861). 53% (Obs) and 59% (WBRT) pts were alive at 12 months. There was no significant between-group difference in mean intervention effect on global QoL (p = 0.083). Pts who received T-cell checkpoint inhibitors and/or mitogen-activated protein kinase (MAPK) pathway inhibitors and WBRT before or within 12 months of randomization had DIF rate 29% compared with Obs and no systemic therapy had 44%, but was not significant (p = 0.228). Obs had greater relative improvement from baseline in HVLT-R at every timepoint. At 4 months, Obs had 20.9% improvement from baseline in HVLT-R-delayed recall compared to 2.7% decline in WBRT; overall adjusted average intervention effect 23.6% (95%CI 9.0, 38.2; p = 0.0018). There was no difference in time to cognitive failure or in proportions with global cognitive impairment. Conclusion: This level one evidence shows WBRT does not improve outcomes in MBMs. This practice-changing trial justifies the recent move away from WBRT that occurred during the course of the trial. Clinical trial information: NCT01503827