BAP1 loss by immunohistochemistry predicts improved survival to first line platinum/pemetrexed chemotherapy for pleural mesothelioma patients: A validation study

Journal of Thoracic Oncology 2022 April 27 [Link]

Amber Louw, Vasiliki Panou, Weronika Maria Szejniuk, Christos Meristoudis, Siaw Ming Chai, Chris van Vliet, Y C Gary Lee, Ian M Dick, Tina Firth, Louise Andersen Lynggaard, Azadeh Birbaneh Asghari, Mogens Vyberg, Johnni Hansen, Jenette Creaney, Oluf Dimitri Røe


Introduction: Pleural mesothelioma (PM) is an aggressive malignancy with no identified predictive biomarkers. We assessed whether tumour BRCA associated protein 1 (BAP1) status is a predictive biomarker for survival in patients receiving first-line combination platinum/pemetrexed therapy.introduction METHODS: PM cases (n=114) from Aalborg, Denmark were stained for BAP1 on tissue microarrays. Demographic, clinical and survival data were extracted from registries and medical records. Surgical cases were excluded. BAP1 status was associated with overall survival (OS) by Cox regression and Kaplan-Meier methods. Results were validated in an independent cohort from Perth, Australia (n=234).

Results: BAP1 loss was demonstrated in 62% and 60.3% of all Danish and Australian samples respectively. BAP1 loss was an independent predictor of OS in multivariate analyses corrected for histology, performance status, age, sex and treatment (HR = 2.49, p < 0.001 and 1.48, p = 0.01, respectively). First-line platinum/pemetrexed treated patients with BAP1 loss had significantly longer median survival than those with retained BAP1 in both the Danish (20.1 vs 7.3 months, p < 0.001) and Australian cohorts (19.6 vs 11.1 months, p < 0.01). Survival in patients with BAP1 retained and treated with platinum/pemetrexed was similar as in those with best supportive care (BSC). There was a higher OS in BSC patients with BAP1 loss, but significant only in the Australian cohort (16.8 vs 8.3 months, p < 0.01).results CONCLUSION: BAP1 is a predictive biomarker for survival following first-line combination platinum/pemetrexed chemotherapy and a potential prognostic marker in PM. BAP1 in tumour is a promising clinical tool for treatment stratification.