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Oncol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Little is known regarding the outcomes of systemic treatments in BAP1-altered malignant pleural mesothelioma (MPM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Forty five patients with MPM [group A: eight MPM patients with BAP1 inactivating mutation\/copy number loss (FoundationOne<jats:sup>\u00ae<\/jats:sup> CDx\/TEMPUSxT), selected from the electronic databases of four Israeli cancer centers (ICC); group B: 37 consecutive (years 2016\u20132018) MPM patients selected from the electronic databases of two ICC\u2014of those six patients without a BAP1 alteration (group B1) and 31 patients not tested for BAP1 (group B2)] were analyzed for ORR, PFS (mRECIST), and OS with 1<jats:sup>st<\/jats:sup>-line platinum\/pemetrexed+\/\u2212antiangiogenic drug (CT, n-28), immune check-point inhibitors (ICPi, n-16) and poly (ADP-ribose) polymerase inhibitors (PARPi, n-4). OS since diagnosis (OSDx) was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There were no differences in ORR or mPFS with CT between the groups: ORR-50% <jats:italic>vs<\/jats:italic>. 47% <jats:italic>vs<\/jats:italic>. 50% <jats:italic>vs<\/jats:italic>. 47% (p&amp;gt;0.9), mPFS-9.1mo (95% CI, 1.2\u201316.1) <jats:italic>vs<\/jats:italic>. 9.2mo (95% CI, 2.9\u201313.3) <jats:italic>vs<\/jats:italic>. 7.2mo (95%\u00a0CI, 2.3-NR) <jats:italic>vs<\/jats:italic>. 10.9mo (95%\u00a0CI, 2.9\u201320.3) (p&amp;gt;0.8) in groups A, B, B1, and B2, respectively. There were no differences in ORR or mPFS with ICPi between the groups: ORR-0% <jats:italic>vs<\/jats:italic>. 27% <jats:italic>vs<\/jats:italic>. 33% <jats:italic>vs<\/jats:italic>. 25% (p&amp;gt;0.2), mPFS-2.5mo (95% CI, 1.4\u20133.7) <jats:italic>vs<\/jats:italic>. 3.0mo (95% CI, 1.3\u201310.5) <jats:italic>vs<\/jats:italic>. 2.0mo (95%\u00a0CI, 1.9-NR) <jats:italic>vs<\/jats:italic>. 4.5mo (95%\u00a0CI, 0.3\u201310.5) (p&amp;gt;0.3) in groups A, B, B1, and B2, respectively. In group A, no responses were seen with PARPi; mPFS with PARPi was 1.8mo (95% CI, 1.8-NR). OSDx was 98.3mo (95%\u00a0CI, 9.7\u201398.3) <jats:italic>vs<\/jats:italic>. 19.4mo (95%\u00a0CI, 9.7\u201347.3) <jats:italic>vs<\/jats:italic>. 18.8mo (95%\u00a0CI, 8.5-NR) <jats:italic>vs<\/jats:italic>. 19.5mo (95%\u00a0CI, 8.3\u201382.2) in groups A, B, B1, and B2, respectively (p&amp;gt;0.3).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>BAP1-altered MPM, as compared to non-selected MPM, is characterized by similar efficacy of CT and ICPi. Numerically longer OS in BAP1-altered MPM may reflect favorable tumor biology. No responses were observed with PARPi.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2021.603223","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T05:45:10Z","timestamp":1615355110000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["BAP1-Altered Malignant Pleural Mesothelioma: Outcomes With Chemotherapy, Immune Check-Point Inhibitors and Poly(ADP-Ribose) Polymerase 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