Retrospective Evaluation of the Use of Pembrolizumab in Malignant Mesothelioma in a Real-World Australian Population.

BAP1 Immunotherapy Mesothelioma PD-L1 Pembrolizumab Tumor-infiltrating lymphocytes

Journal

JTO clinical and research reports
ISSN: 2666-3643
Titre abrégé: JTO Clin Res Rep
Pays: United States
ID NLM: 101769967

Informations de publication

Date de publication:
Nov 2020
Historique:
received: 25 05 2020
revised: 06 07 2020
accepted: 09 07 2020
entrez: 30 9 2021
pubmed: 16 7 2020
medline: 16 7 2020
Statut: epublish

Résumé

We investigated the efficacy and toxicity of pembrolizumab in patients with mesothelioma from a real-world Australian population. We aimed to determine clinical factors and predictive biomarkers that could help select patients who are likely to benefit from pembrolizumab. Patients with mesothelioma who were treated with pembrolizumab as part of the Insurance and Care New South Wales compensation scheme were included. Clinical information was collected retrospectively. Tumor biomarkers such as programmed death-ligand 1 (PD-L1), BAP1, and CD3-positive (CD3+) tumor-infiltrating lymphocytes (TILs) were examined using archival formalin-fixed paraffin-embedded tumor samples. A total of 98 patients were included with a median age of 70 years (range, 46-91 y); 92% were men; 76% had epithelioid subtype; 21% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0. Pembrolizumab was used as second-line or subsequent-line treatment in 94 patients and as first-line treatment in four patients. The overall response rate was 18%, and the disease control rate was 56%. The median progression-free survival (PFS) was 4.8 months (95% confidence interval: 3.6-6.2), and the median overall survival (OS) was 9.5 months (95% confidence interval: 6.6-13.7). Immune-related adverse events occurred in 27% of patients, of which nine (9%) were of grade 3 or higher. In the multivariable analysis, factors independently associated with longer PFS included baseline ECOG status of 0 (median PFS: 12 mo versus 4 mo, Immunotherapy is a reasonable treatment option for patients with mesothelioma. Our results are comparable to other clinical trials investigating pembrolizumab in mesothelioma in terms of response. Good performance status assessment remains the most robust predictor for patient outcomes. CD3+ TILs in the tumor may help select patients that are likely to respond to pembrolizumab, whereas factors such as PD-L1 expression, baseline platelet count, and lack of pretreatment dexamethasone may help predict survival outcomes from pembrolizumab treatment.

Identifiants

DOI: 10.1016/j.jtocrr.2020.100075 PMID: 34589956 PMC: PMC8474198
pubmed: 34589956
doi: 10.1016/j.jtocrr.2020.100075
pii: S2666-3643(20)30098-9
pmc: PMC8474198
doi:

Types de publication

Journal Article

Langues

eng

Pagination

100075

Informations de copyright

© 2020 The Authors.

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Auteurs

Tamkin Ahmadzada (T)

Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.

Wendy A Cooper (WA)

Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Tissue Pathology and Diagnostic Oncology, New South Wales Health Pathology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
School of Medicine, Western Sydney University, Sydney, New South Wales, Australia.

Mikaela Holmes (M)

Tissue Pathology and Diagnostic Oncology, New South Wales Health Pathology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.

Annabelle Mahar (A)

Tissue Pathology and Diagnostic Oncology, New South Wales Health Pathology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.

Helen Westman (H)

Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales, Australia.

Anthony J Gill (AJ)

Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, New South Wales, Australia.

Ina Nordman (I)

Department of Medical Oncology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia.
School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.

Po Yee Yip (PY)

Department of Medical Oncology, Macarthur Cancer Therapy Centre, Campbelltown, New South Wales, Australia.
School of Medicine, Western Sydney University, Sydney, New South Wales, Australia.

Abhijit Pal (A)

School of Medicine, Western Sydney University, Sydney, New South Wales, Australia.
Drug Development Unit, Royal Marsden Hospital, Sutton, United Kingdom.

Rob Zielinski (R)

Central West Cancer Care Centre, Orange Base Hospital, Orange, New South Wales, Australia.
School of Medicine, Western Sydney University, New South Wales, Australia.

Nick Pavlakis (N)

Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales, Australia.
Department of Medical Oncology, Royal North Shore Hospital, The University of Sydney, Sydney, New South Wales, Australia.

Adnan Nagrial (A)

Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Medical Oncology Department, Westmead Hospital, New South Wales, Australia.

Dariush Daneshvar (D)

Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Department of Tissue Pathology and Diagnostic Oncology, Institute of Clinical Pathology & Medical Research (ICPMR)-Westmead Hospital, Sydney, New South Wales, Australia.

Daniel Brungs (D)

Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia.
Illawarra Cancer Centre, Wollongong Hospital, Wollongong, New South Wales, Australia.

Deme Karikios (D)

Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Nepean Cancer Care Centre, Nepean Hospital, Kingswood, New South Wales, Australia.

Vesna Aleksova (V)

Asbestos Diseases Research Institute, Sydney, New South Wales, Australia.

Juliet Burn (J)

Anatomical Pathology, Douglass Hanly Moir Pathology, Sydney, New South Wales, Australia.

Rebecca Asher (R)

National Health and Medical Research Council Clinical Trials Centre, Camperdown, New South Wales, Australia.

Georges E Grau (GE)

Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Vascular Immunology Unit, Department of Pathology, School of Medical Sciences, The University of Sydney, Camperdown, New South Wales, Australia.
The Sydney Nano Institute, The University of Sydney, Camperdown, New South Wales, Australia.

Elham Hosseini-Beheshti (E)

Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Vascular Immunology Unit, Department of Pathology, School of Medical Sciences, The University of Sydney, Camperdown, New South Wales, Australia.

Glen Reid (G)

Department of Pathology, University of Otago, Dunedin, New Zealand.

Stephen Clarke (S)

Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Department of Medical Oncology, Royal North Shore Hospital, The University of Sydney, Sydney, New South Wales, Australia.

Steven Kao (S)

Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Asbestos Diseases Research Institute, Sydney, New South Wales, Australia.
Department of Medical Oncology, Chris O'Brien Lifehouse, Sydney, New South Wales, Australia.

Classifications MeSH