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

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-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% . 47% . 50% . 47% (p>0.9), mPFS-9.1mo (95% CI, 1.2-16.1) . 9.2mo (95% CI, 2.9-13.3) . 7.2mo (95% CI, 2.3-NR) . 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% . 27% . 33% . 25% (p>0.2), mPFS-2.5mo (95% CI, 1.4-3.7) . 3.0mo (95% CI, 1.3-10.5) . 2.0mo (95% CI, 1.9-NR) . 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) . 19.4mo (95% CI, 9.7-47.3) . 18.8mo (95% CI, 8.5-NR) . 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.