BAP1-Altered Malignant Pleural Mesothelioma: Outcomes With Chemotherapy, Immune Check-Point Inhibitors and Poly(ADP-Ribose) Polymerase Inhibitors
Elizabeth Dudnik, Jair Bar, Assaf Moore, Teodor Gottfried, Mor Moskovitz, Julia Dudnik, Tzippy Shochat, Aaron M. Allen, Alona Zer, Ofer Rotem, Nir Peled, Damien Urban
Abstract
Objectives Little is known regarding the outcomes of systemic treatments in BAP1-altered malignant pleural mesothelioma (MPM). Materials and Methods Forty five patients with MPM [group A: eight MPM patients with BAP1 inactivating mutation/copy number loss (FoundationOne ® 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 st -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. Results There were no differences in ORR or mPFS with CT between the groups: ORR-50% vs . 47% vs . 50% vs . 47% (p>0.9), mPFS-9.1mo (95% CI, 1.2–16.1) vs . 9.2mo (95% CI, 2.9–13.3) vs . 7.2mo (95% CI, 2.3-NR) vs . 10.9mo (95% CI, 2.9–20.3) (p>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% vs . 27% vs . 33% vs . 25% (p>0.2), mPFS-2.5mo (95% CI, 1.4–3.7) vs . 3.0mo (95% CI, 1.3–10.5) vs . 2.0mo (95% CI, 1.9-NR) vs . 4.5mo (95% CI, 0.3–10.5) (p>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) vs . 19.4mo (95% CI, 9.7–47.3) vs . 18.8mo (95% CI, 8.5-NR) vs . 19.5mo (95% CI, 8.3–82.2) in groups A, B, B1, and B2, respectively (p>0.3). Conclusions 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.