Retrospective evaluation of the use of pembrolizumab in malignant mesothelioma in a real-world Australian population

Abstract Objectives We investigated the efficacy and toxicity of pembrolizumab in mesothelioma patients 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. Method Mesothelioma patients who were treated with pembrolizumab as part of the iCARE NSW compensation scheme were included. Clinical information was collected retrospectively. Tumor biomarkers such as programmed death-ligand 1 (PD-L1), BRCA1 associated protein-1 (BAP1) and tumor infiltrating lymphocytes (CD3+ TILs) were examined using archival formalin-fixed paraffin-embedded tumor samples. Results A total of 98 patients were included: median age 70 years (range, 46-91); 92% male; 76% epithelioid subtype; 21% Eastern Cooperative Oncology Group (ECOG) Performance Status 0. Pembrolizumab was used as second or subsequent line treatment in 94 patients and as first line treatment in 4 patients. The overall response rate (ORR) was 18% and the disease control rate was 56%. The median progression-free survival (PFS) was 4.8 months (95% CI: 3.6-6.2) and the median overall survival (OS) was 9.5 months (95% CI: 6.6-13.7). Immune-related adverse events (irAEs) occurred in 27% of patients, of which 9 (9%) were of grade 3 or higher. In the multivariable analysis, factors independently associated with longer PFS included baseline ECOG status 0 (median PFS: 12 vs 4 months, p Conclusion Immunotherapy is a reasonable treatment option for mesothelioma patients. 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 outcome. 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 absence of pre-treatment dexamethasone may help predict survival outcomes from pembrolizumab treatment.