AUTHOR=Dudnik Elizabeth , Bar Jair , Moore Assaf , Gottfried Teodor , Moskovitz Mor , Dudnik Julia , Shochat Tzippy , Allen Aaron M. , Zer Alona , Rotem Ofer , Peled Nir , Urban Damien 

TITLE=BAP1-Altered Malignant Pleural Mesothelioma: Outcomes With Chemotherapy, Immune Check-Point Inhibitors and Poly(ADP-Ribose) Polymerase Inhibitors

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.603223

DOI=10.3389/fonc.2021.603223

ISSN=2234-943X

ABSTRACT=<sec><title>Objectives</title><p>Little is known regarding the outcomes of systemic treatments in BAP1-altered malignant pleural mesothelioma (MPM).</p></sec><sec><title>Materials and Methods</title><p>Forty five patients with MPM [group A: eight MPM patients with BAP1 inactivating mutation/copy number loss (FoundationOne<sup>®</sup> CDx/TEMPUSxT), selected from the electronic databases of four Israeli cancer centers (ICC); group B: 37 consecutive (years 2016–2018) MPM patients selected from the electronic databases of two ICC—of 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<sup>st</sup>-line platinum/pemetrexed+/−antiangiogenic 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.</p></sec><sec><title>Results</title><p>There were no differences in ORR or mPFS with CT between the groups: ORR-50% <italic>vs</italic>. 47% <italic>vs</italic>. 50% <italic>vs</italic>. 47% (p&gt;0.9), mPFS-9.1mo (95% CI, 1.2–16.1) <italic>vs</italic>. 9.2mo (95% CI, 2.9–13.3) <italic>vs</italic>. 7.2mo (95% CI, 2.3-NR) <italic>vs</italic>. 10.9mo (95% CI, 2.9–20.3) (p&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% <italic>vs</italic>. 27% <italic>vs</italic>. 33% <italic>vs</italic>. 25% (p&gt;0.2), mPFS-2.5mo (95% CI, 1.4–3.7) <italic>vs</italic>. 3.0mo (95% CI, 1.3–10.5) <italic>vs</italic>. 2.0mo (95% CI, 1.9-NR) <italic>vs</italic>. 4.5mo (95% CI, 0.3–10.5) (p&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% CI, 9.7–98.3) <italic>vs</italic>. 19.4mo (95% CI, 9.7–47.3) <italic>vs</italic>. 18.8mo (95% CI, 8.5-NR) <italic>vs</italic>. 19.5mo (95% CI, 8.3–82.2) in groups A, B, B1, and B2, respectively (p&gt;0.3).</p></sec><sec><title>Conclusions</title><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.</p></sec>