Precision-guided treatment in high-risk pediatric cancers

Loretta M S Lau; Dong-Anh Khuong-Quang; Chelsea Mayoh; Marie Wong; Paulette Barahona; Pamela Ajuyah; Akanksha Senapati; Sumanth Nagabushan; Alexandra Sherstyuk; Ann-Kristin Altekoester; Noemi A Fuentes-Bolanos; Veronica Yeung; Ashleigh Sullivan; Natacha Omer; Yonatan Diamond; Sophie Jessop; Lauren Battaglia; Nataliya Zhukova; Louise Cui; Angela Lin; Andrew J Gifford; Emmy D G Fleuren; Luciano Dalla-Pozza; Andrew S Moore; Seong-Lin Khaw; David D Eisenstat; Nicholas G Gottardo; Paul J Wood; Heather Tapp; Frank Alvaro; Geoffrey McCowage; Wayne Nicholls; Jordan R Hansford; Neevika Manoharan; Rishi S Kotecha; Marion K Mateos; Richard B Lock; Vanessa Tyrrell; Michelle Haber; Toby N Trahair; Mark J Cowley; Paul G Ekert; Glenn M Marshall; David S Ziegler

doi:10.1038/s41591-024-03044-0

Precision-guided treatment in high-risk pediatric cancers

Nat Med. 2024 Jul;30(7):1913-1922. doi: 10.1038/s41591-024-03044-0. Epub 2024 Jun 6.

Authors

Loretta M S Lau^{1

2

3}, Dong-Anh Khuong-Quang^{4

5}, Chelsea Mayoh^{1

2}, Marie Wong^{1

2}, Paulette Barahona¹, Pamela Ajuyah¹, Akanksha Senapati³, Sumanth Nagabushan^{2

3}, Alexandra Sherstyuk¹, Ann-Kristin Altekoester¹, Noemi A Fuentes-Bolanos^{1

2

3}, Veronica Yeung³, Ashleigh Sullivan⁶, Natacha Omer^{6

7}, Yonatan Diamond⁴, Sophie Jessop^{1

8}, Lauren Battaglia⁹, Nataliya Zhukova^{9

10

11}, Louise Cui¹, Angela Lin¹, Andrew J Gifford^{1

2

12}, Emmy D G Fleuren^{1

2}, Luciano Dalla-Pozza¹³, Andrew S Moore⁶, Seong-Lin Khaw^{4

5}, David D Eisenstat^{4

5}, Nicholas G Gottardo^{14

15}, Paul J Wood^{9

10

11}, Heather Tapp⁸, Frank Alvaro¹⁶, Geoffrey McCowage¹³, Wayne Nicholls^{6

7}, Jordan R Hansford^{4

5

8

17

18

19}, Neevika Manoharan^{1

2

3}, Rishi S Kotecha^{14

15

20}, Marion K Mateos^{1

2

3}, Richard B Lock^{1

2

21}, Vanessa Tyrrell^{1

2}, Michelle Haber^{1

2}, Toby N Trahair^{1

2

3}, Mark J Cowley^{1

2}, Paul G Ekert^{1

2

5

22}, Glenn M Marshall^#^{1

2

3}, David S Ziegler^#^{23

24

25}

Affiliations

¹ Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia.
² School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Sydney, New South Wales, Australia.
³ Kids Cancer Centre, Sydney Children's Hospital, Sydney, New South Wales, Australia.
⁴ Children's Cancer Centre, Royal Children's Hospital, Melbourne, Victoria, Australia.
⁵ Department of Paediatrics, Murdoch Children's Research Institute, University of Melbourne, Melbourne, Victoria, Australia.
⁶ Oncology Services Group, Children's Health Queensland Hospital & Health Service, Brisbane, Queensland, Australia.
⁷ Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
⁸ Michael Rice Centre for Haematology and Oncology, Women's and Children's Hospital, Adelaide, South Australia, Australia.
⁹ Children's Cancer Centre, Monash Children's Hospital, Melbourne, Victoria, Australia.
¹⁰ Centre for Cancer Research, Hudson Institute of Medical Research, Melbourne, Victoria, Australia.
¹¹ Department of Paediatrics, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia.
¹² Anatomical Pathology, NSW Health Pathology, Prince of Wales Hospital, Sydney, New South Wales, Australia.
¹³ Cancer Centre for Children, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
¹⁴ Department of Paediatric and Adolescent Oncology and Haematology, Perth Children's Hospital, Perth, Western Australia, Australia.
¹⁵ Telethon Kids Cancer Centre, Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
¹⁶ Children's Cancer and Blood Disorders, John Hunter Children's Hospital, University of Newcastle, Newcastle, New South Wales, Australia.
¹⁷ Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.
¹⁸ South Australia Health and Medical Research Institute, Adelaide, South Australia, Australia.
¹⁹ South Australian immunoGENomics Cancer Institute, University of Adelaide, Adelaide, South Australia, Australia.
²⁰ Curtin Medical School, Curtin University, Perth, Western Australia, Australia.
²¹ UNSW Centre for Childhood Cancer Research, UNSW Sydney, Sydney, New South Wales, Australia.
²² Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
²³ Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, New South Wales, Australia. d.ziegler@unsw.edu.au.
²⁴ School of Clinical Medicine, UNSW Medicine & Health, UNSW Sydney, Sydney, New South Wales, Australia. d.ziegler@unsw.edu.au.
²⁵ Kids Cancer Centre, Sydney Children's Hospital, Sydney, New South Wales, Australia. d.ziegler@unsw.edu.au.

^# Contributed equally.

Abstract

Recent research showed that precision medicine can identify new treatment strategies for patients with childhood cancers. However, it is unclear which patients will benefit most from precision-guided treatment (PGT). Here we report consecutive data from 384 patients with high-risk pediatric cancer (with an expected cure rate of less than 30%) who had at least 18 months of follow-up on the ZERO Childhood Cancer Precision Medicine Program PRecISion Medicine for Children with Cancer (PRISM) trial. A total of 256 (67%) patients received PGT recommendations and 110 (29%) received a recommended treatment. PGT resulted in a 36% objective response rate and improved 2-year progression-free survival compared with standard of care (26% versus 12%; P = 0.049) or targeted agents not guided by molecular findings (26% versus 5.2%; P = 0.003). PGT based on tier 1 evidence, PGT targeting fusions or commenced before disease progression had the greatest clinical benefit. Our data show that PGT informed by comprehensive molecular profiling significantly improves outcomes for children with high-risk cancers. ClinicalTrials.gov registration: NCT03336931.

MeSH terms

Adolescent
Child
Child, Preschool
Female
Humans
Infant
Male
Neoplasms* / drug therapy
Neoplasms* / genetics
Neoplasms* / therapy
Precision Medicine* / methods
Progression-Free Survival
Treatment Outcome

Associated data

ClinicalTrials.gov/NCT03336931

Abstract

MeSH terms

Associated data

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