Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2019

Phase 3 international trial of adjuvant whole brain radiotherapy (WBRT) or observation (Obs) following local treatment of 1-3 melanoma brain metastases (MBMs). (#125)

Gerald B Fogarty 1 2 , Kari Dolven-Jacobsen 3 , Rachael L Morton 2 4 , George Hruby 5 6 , Anna K Nowak 7 , Janette L Vardy 8 , Kate J Drummond 9 10 , Haryana M Dhillon 8 , Catherine Mandel 11 , Richard A Scolyer 2 12 , Brindha Shivalingam 12 , Mark R Middleton 13 , Bryan Burmeister 14 , Daniel E Roos 15 16 , Serigne N Lo 8 17 , Claudius H Reisse 3 , Elizabeth J Paton 8 18 , Narelle C Williams 8 18 , John F Thompson 2 19 , Angela Hong 2 20
  1. Genesis Care, Darlinghurst, NSW, Australia
  2. Melanoma Institute Australia, Sydney, New South Wales, Australia
  3. Oslo University Hospital, Oslo, Norway
  4. NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia
  5. Royal North Shore Hospital, Sydney, New South Wales, Australia
  6. Genesis Care, Sydney, NSW, Australia
  7. Medical School, University of Western Australia, Perth, WA, Australia
  8. Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
  9. Department of Neurosurgery, Royal Melbourne Hospital, Parkville, VIC, Australia
  10. Department of Surgery, University of Melbourne, Melbourne, VIC, Australia
  11. Swinburne University of Technology, Melbourne, VIC, Australia
  12. Royal Prince Alfred Hospital, Sydney, NSW, Australia
  13. University of Oxford, Oxford, United Kingdom
  14. Genesis Care, Hervey Bay, QLD, Australia
  15. Royal Adelaide Hospital, Adelaide, SA, Australia
  16. University of Adelaide, Adelaide, SA, Australia
  17. Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
  18. Australia and New Zealand Melanoma Trials Group, Sydney, NSW, Australia
  19. Department of Melanoma and Surgical Oncology, Royal prince Alfred Hospital, Sydney, NSW, Australia
  20. Mater Hospital, Sydney, NSW, Australia

Aims:

The role of adjuvant WBRT in MBMs is controversial. This randomised 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 randomisation. The a priori neurocognitive function (NCF) endpoint is Hopkins Verbal Learning Test-Revised (HVLT-R) delayed recall at 4 months and is reported separately. 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 randomised 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 randomisation. The two arms were well matched.

Within 12 months, 54 (50.5%) Obs pts 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 kinases (MAPK) pathway inhibitors and WBRT before or within 12 months of randomisation had DIF rate 29% compared with Obs and no systemic therapy had 44%, but was not significant (p=0.228).

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.