Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/34338
Title: The features and management of acquired resistance to PD1-based therapy in metastatic melanoma.
Austin Authors: Hepner, Adriana;Versluis, Judith M;Wallace, Roslyn;Allayous, Clara;Brown, Lauren Julia;Trojaniello, Claudia;Gerard, Camille Lea;Jansen, Yanina Jl;Bhave, Prachi;Neyns, Bart;Haydon, Andrew;Michielin, Olivier;Mangana, Joanna;Klein, Oliver ;Shoushtari, Alexander N;Warner, Allison Betof;Ascierto, Paolo Antonio;McQuade, Jennifer Leigh;Carlino, Matteo S;Zimmer, Lisa;Lebbe, Celeste;Johnson, Douglas B;Sandhu, Shahneen;Atkinson, Victoria;Blank, Christian U;Lo, Serigne N;Long, Georgina V;Menzies, Alexander M
Affiliation: 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.
Université Paris Cite, Dermato-Oncology AP-HP Hôpital 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.
Sir Peter MacCallum Cancer Centre Department of Oncology, The University of Melbourne, Melbourne, Australia; Department of Medical Oncology, Alfred Health, Melbourne, Australia.
Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
Department of Medical Oncology, Alfred Health, Melbourne, Australia; Monash University, Melbourne, Australia.
Precision Oncology Center Oncology department, Lausanne University Hospital CHUV, Lausanne, Switzerland.
University Hospital Zürich, Zürich, Switzerland.
Olivia Newton-John Cancer Wellness and Research Centre
Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy.
The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Dermatology, University Hospital Essen, Essen, Germany.
Université Paris Cite, Dermato-Oncology AP-HP Hôpital Saint Louis, INSERM U976, F-75010 Paris, France.
Department of Medicine, Vanderbilt University Medical Center, Nashville TN, USA.
Sir Peter MacCallum Cancer Centre Department of Oncology, The University of Melbourne, Melbourne, Australia; University of Melbourne, Melbourne, Australia.
University of Queensland and Princess Alexandra and Greenslopes Private Hospital, Brisbane, Australia.
Netherlands Cancer Institute (NKI), Amsterdam, the Netherlands; Leiden University Medical Center (LUMC), Leiden, the Netherlands.
Melanoma Institute Australia, The University of Sydney, NSW, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
Issue Date: 20-Nov-2023
Date: 2023
Publication information: European Journal of Cancer (Oxford, England : 1990) 2023-11-20; 196
Abstract: 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. Pts from 16 centres who responded to PD1-based therapy and who later progressed were examined. Demographics, disease characteristics and subsequent treatments were evaluated. 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). Acquired resistance to PD1 therapy in melanoma is largely oligometastatic, and pts may have a favorable survival outcome following salvage treatment.
URI: https://ahro.austin.org.au/austinjspui/handle/1/34338
DOI: 10.1016/j.ejca.2023.113441
ORCID: 
Journal: European Journal of Cancer (Oxford, England : 1990)
Start page: 113441
PubMed URL: 37988842
ISSN: 1879-0852
Type: Journal Article
Subjects: Cytotoxic T-Lymphocyte Antigen 4
Disease Progression
Immunotherapy
Melanoma
Programmed death-1
Resistance
Appears in Collections:Journal articles

Show full item record

Page view(s)

40
checked on Feb 25, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.