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Title: | The features and management of acquired resistance to PD1-based therapy in metastatic melanoma |
Authors: | Hepner, A.;Versluis, M.;Wallace, R.;Allayous, C.;Brown, Lauren J.;Trojaniello, C.;Gerard, C. L.;Jansen, Y. J.;Bhave, P.;Neyns, B.;Haydon, A.;Michielin, O.;Mangana, J.;Klein, O.;Shoushtari, A. N.;Warner, A. B.;Ascierto, P. A.;McQuade, J. L.;Carlino, Matteo S.;Zimmer, L.;Lebbe, C.;Johnson, D. B.;Sandhu, S.;Atkinson, V.;Blank, C. U.;Lo, S. N.;Long, G. V.;Menzies, A. M. |
WSLHD Author: | Brown, Lauren J.;Carlino, Matteo S. |
Subjects: | Oncology |
Issue Date: | 2024 |
Citation: | European Journal of Cancer 196:113441, 2024 |
Abstract: | BACKGROUND: Anti-PD-1 therapy (PD1) either alone or with anti-CTLA-4 (CTLA4), has high initial response rates, however 20% of patients (pts) with complete response (CR) and 30% with partial response (PR) within 12 months of treatment experience subsequent disease progression by 6 years. The nature and optimal management of this acquired resistance (AR) remains unknown., METHODS: Pts from 16 centres who responded to PD1-based therapy and who later progressed were examined. Demographics, disease characteristics and subsequent treatments were evaluated., RESULTS: 299 melanoma pts were identified, median age 64y, 44% BRAFV600m. 172 (58%) received PD1 alone, 114 (38%) PD1/CTLA4 and 13 (4%) PD1 and an investigational drug. 90 (30%) pts had CR, 209 (70%) PR. Median time to AR was 12.6 mo (95% CI, 11.3, 14.2). Most (N = 193, 65%) progressed in a single organ site, and in a solitary lesion (N = 151, 51%). The most frequent sites were lymph nodes (38%) and brain (25%). Management at AR included systemic therapy (ST, 45%), local therapy (LT) +ST (31%), LT alone (21%), or observation (3%). There was no statistical difference in PFS2 or OS based on management, however, PFS2 was numerically superior for pts treated with ST alone who progressed off PD1 therapy than those who progressed on PD1 (2-year PFS2 42% versus 25%, p = 0.249). mOS from AR was 38.0 months (95% CI, 29.5-NR); longer in single-site versus multi-site progression (2-year OS 70% vs 54%, p < 0.001)., CONCLUSIONS: Acquired resistance to PD1 therapy in melanoma is largely oligometastatic, and pts may have a favorable survival outcome following salvage treatment. |
URI: | https://wslhd.intersearch.com.au/wslhdjspui/handle/1/8357 |
DOI: | https://dx.doi.org/10.1016/j.ejca.2023.113441 |
Journal: | European Journal of Cancer |
Type: | Journal Article |
Study or Trial: | Retrospective Study |
Department: | Oncology |
Facility: | Blacktown Westmead |
Affiliated Organisations: | Melanoma Institute Australia, The University of Sydney, NSW, Australia Instituto do Cancer do Estado de Sao Paulo, SP, Brazil Netherlands Cancer Institute (NKI), Amsterdam, the Netherlands Sir Peter MacCallum Cancer Centre Department of Oncology, The University of Melbourne, Melbourne, Australia Universit? Paris Cite, Dermato-Oncology AP-HP H?pital Saint Louis, INSERM U976, F-75010 Paris, France Crown Princess Mary Cancer Centre Westmead and Blacktown Hospitals, Sydney, Australia Faculty of Medicine and Health, The University of Sydney, Sydney, Australia Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy Precision Oncology Center Oncology department, Lausanne University Hospital CHUV, Lausanne, Switzerland Department of Thoracic Surgery, University Hospitals Leuven, Leuven 3000, Belgium Department of Medical Oncology, Alfred Health, Melbourne, Australia Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Belgium Monash University, Melbourne, Australia University Hospital Zurich, Zurich, Switzerland Olivia Newton-John Cancer Centre and Austin Health, Melbourne, Australia Memorial Sloan Kettering Cancer Center, New York, NY, USA Weill Cornell Medical College, New York, NY, USA The University of Texas MD Anderson Cancer Center, Houston, TX, USA Department of Dermatology, University Hospital Essen, Essen, Germany Department of Medicine, Vanderbilt University Medical Center, Nashville TN, USA University of Melbourne, Melbourne, Australia University of Queensland and Princess Alexandra and Greenslopes Private Hospital, Brisbane, Australia Leiden University Medical Center (LUMC), Leiden, the Netherlands Royal North Shore and Mater Hospitals, NSW, Australia |
Keywords: | Cytotoxic T-Lymphocyte Antigen 4 Disease Progression Immunotherapy Melanoma Programmed death-1 |
Appears in Collections: | Blacktown Mount Druitt Hospital |
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